![conference banner](/images/conference-banner.jpeg)
摘要
丝氨酸蛋白酶在许多生理和病理过程中发挥重要作用,并在许多临床适应症中被证实为诊断和治疗靶点。抑制这些蛋白酶异常的蛋白水解活性已被临床用于相关疾病的治疗。作为丝氨酸蛋白酶的药物调节剂的10-20个残基多肽具有小分子药物和大分子药物的双重特性,倍受人们的关注。本文综述了与单克隆抗体相比具有强抑制和高特异性的抗丝氨酸蛋白酶肽抑制剂的研究进展。此外,我们还讨论了提高肽在体内的半衰期和生物利用度的策略,这是目前限制肽类药物临床转译的主要障碍。本文提出了开发有效的丝氨酸蛋白酶抑制剂的新途径,并强调了这些抑制剂的药用前景。
关键词: 丝氨酸蛋白酶,肽基抑制剂,合理设计,,癌症,血栓,晶体学。
[1]
Mann, K.G. Biochemistry and physiology of blood coagulation. Thromb. Haemost., 1999, 82(2), 165-174.
[PMID: 10605701]
[PMID: 10605701]
[2]
Robbins, K.C. The human plasma fibrinolytic system: regulation and control. Mol. Cell. Biochem., 1978, 20(3), 149-157.
[http://dx.doi.org/10.1007/BF00243761] [PMID: 151804]
[http://dx.doi.org/10.1007/BF00243761] [PMID: 151804]
[3]
Goldberg, A.L.; Rock, K.L. Proteolysis, proteasomes and antigen presentation. Nature, 1992, 357(6377), 375-379.
[http://dx.doi.org/10.1038/357375a0] [PMID: 1317508]
[http://dx.doi.org/10.1038/357375a0] [PMID: 1317508]
[4]
Dano, K.; Romer, J.; Nielsen, B.S.; Bjorn, S.; Pyke, C.; Rygaard, J.; Lund, L.R. Cancer invasion and tissue remodeling-
-cooperation of prote-ase systems and cell types. APMIS,
1999, 1999, 107(1), 120-127.
[http://dx.doi.org/10.1111/j.1699-0463.1999.tb01534.x ] [PMID: 10190288]
[http://dx.doi.org/10.1111/j.1699-0463.1999.tb01534.x ] [PMID: 10190288]
[5]
Whitcomb, D.C.; Lowe, M.E. Human pancreatic digestive enzymes. Dig. Dis. Sci., 2007, 52(1), 1-17.
[http://dx.doi.org/10.1007/s10620-006-9589-z] [PMID: 17205399]
[http://dx.doi.org/10.1007/s10620-006-9589-z] [PMID: 17205399]
[6]
Soualmia, F.; El Amri, C. Serine protease inhibitors to treat inflammation: a patent review (2011-2016). Expert Opin. Ther. Pat., 2018, 28(2), 93-110.
[http://dx.doi.org/10.1080/13543776.2018.1406478] [PMID: 29171765]
[http://dx.doi.org/10.1080/13543776.2018.1406478] [PMID: 29171765]
[7]
Hedstrom, L. Serine protease mechanism and specificity. Chem. Rev., 2002, 102(12), 4501-4524.
[http://dx.doi.org/10.1021/cr000033x] [PMID: 12475199]
[http://dx.doi.org/10.1021/cr000033x] [PMID: 12475199]
[8]
Hames, B.D.; Hooper, N.M.; Hames, B.D. Biochemistry, 3rd ed; Taylor & Francis: New York, N.Y., 2005.
[9]
Kunitz, M. Formation of new crystalline enzymes from chymotrypsin: Isolation of beta and gamma chymotrypsin. J. Gen. Physiol., 1938, 22(2), 207-237.
[http://dx.doi.org/10.1085/jgp.22.2.207] [PMID: 19873101]
[http://dx.doi.org/10.1085/jgp.22.2.207] [PMID: 19873101]
[10]
Matthews, B.W.; Sigler, P.B.; Henderson, R.; Blow, D.M. Three-dimensional structure of tosyl-alpha-chymotrypsin. Nature, 1967, 214(5089), 652-656.
[http://dx.doi.org/10.1038/214652a0] [PMID: 6049071]
[http://dx.doi.org/10.1038/214652a0] [PMID: 6049071]
[11]
Huber, R.; Bode, W. Structural basis of the activation and action of trypsin. Acc. Chem. Res., 1978, 11(3), 71-81.
[http://dx.doi.org/10.1021/ar50123a006]
[http://dx.doi.org/10.1021/ar50123a006]
[12]
Brünger, A.T.; Huber, R.; Karplus, M. Trypsinogen-trypsin transition: a molecular dynamics study of induced conformational change in the activation domain. Biochemistry, 1987, 26(16), 5153-5162.
[http://dx.doi.org/10.1021/bi00390a039] [PMID: 3663651]
[http://dx.doi.org/10.1021/bi00390a039] [PMID: 3663651]
[13]
Furie, B.; Furie, B.C. Formation of the clot. Thromb. Res., 2012, 130(Suppl. 1), S44-S46.
[http://dx.doi.org/10.1016/j.thromres.2012.08.272] [PMID: 23026660]
[http://dx.doi.org/10.1016/j.thromres.2012.08.272] [PMID: 23026660]
[14]
Ten Cate, H.; Hackeng, T.M.; García de Frutos, P. Coagulation factor and protease pathways in thrombosis and cardiovascular disease. Thromb. Haemost., 2017, 117(7), 1265-1271.
[http://dx.doi.org/10.1160/TH17-02-0079] [PMID: 28594052]
[http://dx.doi.org/10.1160/TH17-02-0079] [PMID: 28594052]
[15]
Kolev, K.; Longstaff, C. Bleeding related to disturbed fibrinolysis. Br. J. Haematol., 2016, 175(1), 12-23.
[http://dx.doi.org/10.1111/bjh.14255] [PMID: 27477022]
[http://dx.doi.org/10.1111/bjh.14255] [PMID: 27477022]
[16]
Mangano, D.T.; Layug, E.L.; Wallace, A.; Tateo, I. Multicenter Study of Perioperative Ischemia Research Group. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. N. Engl. J. Med., 1996, 335(23), 1713-1720.
[http://dx.doi.org/10.1056/NEJM199612053352301] [PMID: 8929262]
[http://dx.doi.org/10.1056/NEJM199612053352301] [PMID: 8929262]
[17]
Mullins, D.E.; Rohrlich, S.T. The role of proteinases in cellular invasiveness. Biochim. Biophys. Acta, 1983, 695(3-4), 177-214.
[http://dx.doi.org/10.1016/0304-419X(83)90011-2] [PMID: 6317025]
[http://dx.doi.org/10.1016/0304-419X(83)90011-2] [PMID: 6317025]
[18]
Duffy, M.J.; McGowan, P.M.; Harbeck, N.; Thomssen, C.; Schmitt, M. uPA and PAI-1 as biomarkers in breast cancer: validated for clinical use in level-of-evidence-1 studies. Breast Cancer Res., 2014, 16(4), 428.
[http://dx.doi.org/10.1186/s13058-014-0428-4] [PMID: 25677449]
[http://dx.doi.org/10.1186/s13058-014-0428-4] [PMID: 25677449]
[19]
Andreasen, P.A.; Egelund, R.; Petersen, H.H. The plasminogen activation system in tumor growth, invasion, and metastasis. Cell. Mol. Life Sci., 2000, 57(1), 25-40.
[http://dx.doi.org/10.1007/s000180050497] [PMID: 10949579]
[http://dx.doi.org/10.1007/s000180050497] [PMID: 10949579]
[20]
Mekkawy, A.H.; Pourgholami, M.H.; Morris, D.L. Involvement of urokinase-type plasminogen activator system in cancer: an overview. Med. Res. Rev., 2014, 34(5), 918-956.
[http://dx.doi.org/10.1002/med.21308] [PMID: 24549574]
[http://dx.doi.org/10.1002/med.21308] [PMID: 24549574]
[21]
Hong, S.K. Kallikreins as biomarkers for prostate cancer. Biom.Med Res. Int., 2014, 2014 526341
[http://dx.doi.org/10.1155/2014/526341] [PMID: 24809052]
[http://dx.doi.org/10.1155/2014/526341] [PMID: 24809052]
[22]
Mavridis, K.; Avgeris, M.; Scorilas, A. Targeting kallikrein-related peptidases in prostate cancer. Expert Opin. Ther. Targets, 2014, 18(4), 365-383.
[http://dx.doi.org/10.1517/14728222.2014.880693] [PMID: 24571737]
[http://dx.doi.org/10.1517/14728222.2014.880693] [PMID: 24571737]
[23]
Kryza, T.; Silva, M.L.; Loessner, D.; Heuzé-Vourc’h, N.; Clements, J.A. The kallikrein-related peptidase family: dysregulation and functions during cancer progression. Biochimie, 2016, 122, 283-299.
[http://dx.doi.org/10.1016/j.biochi.2015.09.002] [PMID: 26343558]
[http://dx.doi.org/10.1016/j.biochi.2015.09.002] [PMID: 26343558]
[24]
Wu, Y.; Lu, M.; Zhou, Q. Kallikrein expression as a prognostic factor in ovarian cancer: a systematic review and meta-analysis. J. BUON, 2015, 20(3), 855-861.
[PMID: 26214640]
[PMID: 26214640]
[25]
Schmitt, M.; Jänicke, F.; Moniwa, N.; Chucholowski, N.; Pache, L.; Graeff, H. Tumor-associated urokinase-type plasminogen activator: biological and clinical significance. Biol. Chem. Hoppe Seyler, 1992, 373(7), 611-622.
[http://dx.doi.org/10.1515/bchm3.1992.373.2.611] [PMID: 1515091]
[http://dx.doi.org/10.1515/bchm3.1992.373.2.611] [PMID: 1515091]
[26]
Ramani, V.C.; Kaushal, G.P.; Haun, R.S. Proteolytic action of kallikrein-related peptidase 7 produces unique active matrix metalloproteinase-9 lacking the C-terminal hemopexin domains. Biochim. Biophys. Acta, 2011, 1813(8), 1525-1531.
[http://dx.doi.org/10.1016/j.bbamcr.2011.05.007] [PMID: 21616098]
[http://dx.doi.org/10.1016/j.bbamcr.2011.05.007] [PMID: 21616098]
[27]
Antalis, T.M.; Bugge, T.H.; Wu, Q. Membrane-anchored serine proteases in health and disease. Prog. Mol. Biol. Transl. Sci., 2011, 99, 1-50.
[http://dx.doi.org/10.1016/B978-0-12-385504-6.00001-4] [PMID: 21238933]
[http://dx.doi.org/10.1016/B978-0-12-385504-6.00001-4] [PMID: 21238933]
[28]
Murray, A.S.; Varela, F.A.; List, K. Type II transmembrane serine proteases as potential targets for cancer therapy. Biol. Chem., 2016, 397(9), 815-826.
[http://dx.doi.org/10.1515/hsz-2016-0131] [PMID: 27078673]
[http://dx.doi.org/10.1515/hsz-2016-0131] [PMID: 27078673]
[29]
Uhland, K. Matriptase and its putative role in cancer. Cell. Mol. Life Sci., 2006, 63(24), 2968-2978.
[http://dx.doi.org/10.1007/s00018-006-6298-x] [PMID: 17131055]
[http://dx.doi.org/10.1007/s00018-006-6298-x] [PMID: 17131055]
[30]
Galkin, A.V.; Mullen, L.; Fox, W.D.; Brown, J.; Duncan, D.; Moreno, O.; Madison, E.L.; Agus, D.B. CVS-3983, a selective matriptase inhibitor, suppresses the growth of androgen independent prostate tumor xenografts. Prostate, 2004, 61(3), 228-235.
[http://dx.doi.org/10.1002/pros.20094] [PMID: 15368474]
[http://dx.doi.org/10.1002/pros.20094] [PMID: 15368474]
[31]
Steinmetzer, T.; Schweinitz, A.; Stürzebecher, A.; Dönnecke, D.; Uhland, K.; Schuster, O.; Steinmetzer, P.; Müller, F.; Friedrich, R.; Than, M.E.; Bode, W.; Stürzebecher, J. Secondary amides of sulfonylated 3-amidinophenylalanine. New potent and selective inhibitors of matriptase. J. Med. Chem., 2006, 49(14), 4116-4126.
[http://dx.doi.org/10.1021/jm051272l] [PMID: 16821772]
[http://dx.doi.org/10.1021/jm051272l] [PMID: 16821772]
[32]
Colombo, E.; Désilets, A.; Duchêne, D.; Chagnon, F.; Najmanovich, R.; Leduc, R.; Marsault, E. Design and synthesis of potent, selective inhibitors of matriptase. ACS Med. Chem. Lett., 2012, 3(7), 530-534.
[http://dx.doi.org/10.1021/ml3000534] [PMID: 24900505]
[http://dx.doi.org/10.1021/ml3000534] [PMID: 24900505]
[33]
Gray, K.; Elghadban, S.; Thongyoo, P.; Owen, K.A.; Szabo, R.; Bugge, T.H.; Tate, E.W.; Leatherbarrow, R.J.; Ellis, V. Potent and specific inhibition of the biological activity of the type-II transmembrane serine protease matriptase by the cyclic microprotein MCoTI-II. Thromb. Haemost., 2014, 112(2), 402-411.
[http://dx.doi.org/10.1160/TH13-11-0895] [PMID: 24696092]
[http://dx.doi.org/10.1160/TH13-11-0895] [PMID: 24696092]
[34]
Zuraw, B.L. Clinical practice. Hereditary angioedema. N. Engl. J. Med., 2008, 359(10), 1027-1036.
[http://dx.doi.org/10.1056/NEJMcp0803977] [PMID: 18768946]
[http://dx.doi.org/10.1056/NEJMcp0803977] [PMID: 18768946]
[35]
Schmaier, A.H. Plasma prekallikrein: its role in hereditary angioedema and health and disease. Front. Med. (Lausanne), 2018, 5, 3.
[http://dx.doi.org/10.3389/fmed.2018.00003] [PMID: 29423395]
[http://dx.doi.org/10.3389/fmed.2018.00003] [PMID: 29423395]
[36]
Kaplan, A.P.; Joseph, K. Pathogenic mechanisms of bradykinin mediated diseases: dysregulation of an innate inflammatory pathway. Adv. Immunol., 2014, 121, 41-89.
[http://dx.doi.org/10.1016/B978-0-12-800100-4.00002-7] [PMID: 24388213]
[http://dx.doi.org/10.1016/B978-0-12-800100-4.00002-7] [PMID: 24388213]
[37]
Pizard, A.; Richer, C.; Bouby, N.; Picard, N.; Meneton, P.; Azizi, M.; Alhenc-Gelas, F. Genetic deficiency in tissue kallikrein activity in mouse and man: effect on arteries, heart and kidney. Biol. Chem., 2008, 389(6), 701-706.
[http://dx.doi.org/10.1515/BC.2008.081] [PMID: 18627303]
[http://dx.doi.org/10.1515/BC.2008.081] [PMID: 18627303]
[38]
Craik, C.S.; Page, M.J.; Madison, E.L. Proteases as therapeutics. Biochem. J., 2011, 435(1), 1-16.
[http://dx.doi.org/10.1042/BJ20100965] [PMID: 21406063]
[http://dx.doi.org/10.1042/BJ20100965] [PMID: 21406063]
[39]
Della Valle, P.; Pavani, G.; D’Angelo, A. The protein C pathway and sepsis. Thromb. Res., 2012, 129(3), 296-300.
[http://dx.doi.org/10.1016/j.thromres.2011.11.013] [PMID: 22154246]
[http://dx.doi.org/10.1016/j.thromres.2011.11.013] [PMID: 22154246]
[40]
Griffin, J.H.; Zlokovic, B.V.; Mosnier, L.O. Protein C anticoagulant and cytoprotective pathways. Int. J. Hematol., 2012, 95(4), 333-345.
[http://dx.doi.org/10.1007/s12185-012-1059-0] [PMID: 22477541]
[http://dx.doi.org/10.1007/s12185-012-1059-0] [PMID: 22477541]
[41]
Esmon, C.T. Protein C anticoagulant system--anti-inflammatory effects. Semin. Immunopathol., 2012, 34(1), 127-132.
[http://dx.doi.org/10.1007/s00281-011-0284-6] [PMID: 21822632]
[http://dx.doi.org/10.1007/s00281-011-0284-6] [PMID: 21822632]
[42]
Warren, H.S.; Suffredini, A.F.; Eichacker, P.Q.; Munford, R.S. Risks and benefits of activated protein C treatment for severe sepsis. N. Engl. J. Med., 2002, 347(13), 1027-1030.
[http://dx.doi.org/10.1056/NEJMsb020574] [PMID: 12324562]
[http://dx.doi.org/10.1056/NEJMsb020574] [PMID: 12324562]
[43]
Kylat, R.I.; Ohlsson, A. Recombinant human activated protein C for severe sepsis in neonates. Cochrane Database Syst. Rev., 2012, (4)CD005385
[http://dx.doi.org/10.1002/14651858.CD005385.pub3] [PMID: 22513930]
[http://dx.doi.org/10.1002/14651858.CD005385.pub3] [PMID: 22513930]
[44]
Dellinger, R.P.; Levy, M.M.; Rhodes, A.; Annane, D.; Gerlach, H.; Opal, S.M.; Sevransky, J.E.; Sprung, C.L.; Douglas, I.S.; Jaeschke, R.; Osborn, T.M.; Nunnally, M.E.; Townsend, S.R.; Reinhart, K.; Kleinpell, R.M.; Angus, D.C.; Deutschman, C.S.; Machado, F.R.; Rubenfeld, G.D.; Webb, S.A.; Beale, R.J.; Vincent, J.L.; Moreno, R. Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit. Care Med., 2013, 41(2), 580-637.
[http://dx.doi.org/10.1097/CCM.0b013e31827e83af] [PMID: 23353941]
[http://dx.doi.org/10.1097/CCM.0b013e31827e83af] [PMID: 23353941]
[45]
Angus, D.C.; van der Poll, T. Severe sepsis and septic shock. N. Engl. J. Med., 2013, 369(21), 2063.
[PMID: 24256390]
[PMID: 24256390]
[46]
Medcalf, R.L.; Davis, S.M. Plasminogen activation and thrombolysis for ischemic stroke. Int. J. Stroke, 2012, 7(5), 419-425.
[http://dx.doi.org/10.1111/j.1747-4949.2012.00783.x] [PMID: 22463085]
[http://dx.doi.org/10.1111/j.1747-4949.2012.00783.x] [PMID: 22463085]
[47]
Schwieger, J.; Reiss, R.; Cohen, J.L.; Adler, L.; Makoff, D. Acute renal allograft dysfunction in the setting of deep venous thrombosis: a case of successful urokinase thrombolysis and a review of the literature. Am. J. Kidney Dis., 1993, 22(2), 345-350.
[http://dx.doi.org/10.1016/S0272-6386(12)70330-X] [PMID: 8352265]
[http://dx.doi.org/10.1016/S0272-6386(12)70330-X] [PMID: 8352265]
[48]
Joo, C.U.; Kim, J.S.; Han, Y.M. Mycoplasma pneumoniae induced popliteal artery thrombosis treated with urokinase. Postgrad. Med. J., 2001, 77(913), 723-724.
[http://dx.doi.org/10.1136/pmj.77.913.723] [PMID: 11677283]
[http://dx.doi.org/10.1136/pmj.77.913.723] [PMID: 11677283]
[49]
Andrews, P.J. Critical care management of acute ischemic stroke. Curr. Opin. Crit. Care, 2004, 10(2), 110-115.
[http://dx.doi.org/10.1097/00075198-200404000-00006] [PMID: 15075720]
[http://dx.doi.org/10.1097/00075198-200404000-00006] [PMID: 15075720]
[50]
Christophe, B.R.; Mehta, S.H.; Garton, A.L.; Sisti, J.; Connolly, E.S., Jr Current and future perspectives on the treatment of cerebral ischemia. Expert Opin. Pharmacother., 2017, 18(6), 573-580.
[http://dx.doi.org/10.1080/14656566.2017.1309022] [PMID: 28393614]
[http://dx.doi.org/10.1080/14656566.2017.1309022] [PMID: 28393614]
[51]
Collen, D. Fibrin-specific thrombolytic agents. Arch. Mal. Coeur Vaiss., 1988, 81(Spec No), 19-23.
[PMID: 3142407]
[PMID: 3142407]
[52]
Lippi, G.; Mattiuzzi, C.; Favaloro, E.J. Novel and emerging therapies: thrombus-targeted fibrinolysis. Semin. Thromb. Hemost., 2013, 39(1), 48-58.
[PMID: 23034825]
[PMID: 23034825]
[53]
Minematsu, K.; Toyoda, K.; Hirano, T.; Kimura, K.; Kondo, R.; Mori, E.; Nakagawara, J.; Sakai, N.; Shiokawa, Y.; Tanahashi, N.; Yasaka, M.; Katayama, Y.; Miyamoto, S.; Ogawa, A.; Sasaki, M.; Suga, S.; Yamaguchi, T.; Japan Stroke, S. Guidelines for the intravenous application of recombinant
tissue-type plasminogen activator (alteplase), the
second edi-tion, October 2012: a guideline from the Japan
Stroke Society. J. Stroke Cerebrovasc. Dis, 2013, 22(5), 571-600.
[54]
Fugate, J.E.; Rabinstein, A.A. Update on intravenous recombinant tissue plasminogen activator for acute ischemic stroke. Mayo Clin. Proc., 2014, 89(7), 960-972.
[http://dx.doi.org/10.1016/j.mayocp.2014.03.001] [PMID: 24775222]
[http://dx.doi.org/10.1016/j.mayocp.2014.03.001] [PMID: 24775222]
[55]
Schramm, W. The history of haemophilia - a short review. Thromb. Res., 2014, 134(Suppl. 1), S4-S9.
[http://dx.doi.org/10.1016/j.thromres.2013.10.020] [PMID: 24513149]
[http://dx.doi.org/10.1016/j.thromres.2013.10.020] [PMID: 24513149]
[56]
Berntorp, E.; Shapiro, A.D. Modern haemophilia care. Lancet, 2012, 379(9824), 1447-1456.
[http://dx.doi.org/10.1016/S0140-6736(11)61139-2] [PMID: 22456059]
[http://dx.doi.org/10.1016/S0140-6736(11)61139-2] [PMID: 22456059]
[57]
Hedner, U.; Lee, C.A. First 20 years with recombinant FVIIa (NovoSeven). Haemophilia, 2011, 17(1), e172-e182.
[http://dx.doi.org/10.1111/j.1365-2516.2010.02352.x] [PMID: 20609014]
[http://dx.doi.org/10.1111/j.1365-2516.2010.02352.x] [PMID: 20609014]
[58]
Hodgetts, T.J.; Kirkman, E.; Mahoney, P.F.; Russell, R.; Thomas, R.; Midwinter, M. UK defence medical services guidance for the use of recombinant factor VIIa (rFVIIa) in the deployed military setting. J. R. Army Med. Corps, 2007, 153(4), 307-309.
[http://dx.doi.org/10.1136/jramc-153-04-18] [PMID: 18619169]
[http://dx.doi.org/10.1136/jramc-153-04-18] [PMID: 18619169]
[59]
Buchanan, M.R. Ph. D; Brister, S.J.; Ofosu, F.A. Thrombin: its key role in thrombogenesis: implications for its inhibition clinically, 1st ed; CRC Press, 1994.
[60]
Flaherty, M.J.; Henderson, R.; Wener, M.H. Iatrogenic immunization with bovine thrombin: a mechanism for prolonged thrombin times after surgery. Ann. Intern. Med., 1989, 111(8), 631-634.
[http://dx.doi.org/10.7326/0003-4819-111-8-631] [PMID: 2802417]
[http://dx.doi.org/10.7326/0003-4819-111-8-631] [PMID: 2802417]
[61]
Croxtall, J.D.; Scott, L.J. Recombinant human thrombin: in surgical hemostasis. Bio.Drugs, 2009, 23(5), 333-338.
[http://dx.doi.org/10.2165/11202650-000000000-00000] [PMID: 19754221]
[http://dx.doi.org/10.2165/11202650-000000000-00000] [PMID: 19754221]
[62]
Al-Abdullah, I.H.; Greally, J. C1-inhibitor--biochemical properties and clinical applications. Crit. Rev. Immunol., 1985, 5(4), 317-330.
[PMID: 3899511]
[PMID: 3899511]
[63]
Rao, J.S.; Kahler, C.B.; Baker, J.B.; Festoff, B.W. Protease nexin I, a serpin, inhibits plasminogen-dependent degradation of muscle extracellular matrix. Muscle Nerve, 1989, 12(8), 640-646.
[http://dx.doi.org/10.1002/mus.880120805] [PMID: 2506447]
[http://dx.doi.org/10.1002/mus.880120805] [PMID: 2506447]
[64]
Cunningham, D.D. Regulation of neuronal cells and astrocytes by protease nexin-1 and thrombin. Ann. N. Y. Acad. Sci., 1992, 674, 228-236.
[http://dx.doi.org/10.1111/j.1749-6632.1992.tb27491.x] [PMID: 1288365]
[http://dx.doi.org/10.1111/j.1749-6632.1992.tb27491.x] [PMID: 1288365]
[65]
Huntington, J.A. Serpin structure, function and dysfunction. J. Thromb. Haemost., 2011, 9(Suppl. 1), 26-34.
[http://dx.doi.org/10.1111/j.1538-7836.2011.04360.x] [PMID: 21781239]
[http://dx.doi.org/10.1111/j.1538-7836.2011.04360.x] [PMID: 21781239]
[66]
van Boven, H.H.; Lane, D.A. Antithrombin and its inherited deficiency states. Semin. Hematol., 1997, 34(3), 188-204.
[PMID: 9241705]
[PMID: 9241705]
[67]
DeMeo, D.L.; Silverman, E.K. Alpha1-antitrypsin deficiency. 2: genetic aspects of alpha(1)-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk. Thorax, 2004, 59(3), 259-264.
[http://dx.doi.org/10.1136/thx.2003.006502] [PMID: 14985567]
[http://dx.doi.org/10.1136/thx.2003.006502] [PMID: 14985567]
[68]
Mehta, R.; Shapiro, A.D. Plasminogen activator inhibitor type 1 deficiency. Haemophilia, 2008, 14(6), 1255-1260.
[http://dx.doi.org/10.1111/j.1365-2516.2008.01834.x] [PMID: 19141166]
[http://dx.doi.org/10.1111/j.1365-2516.2008.01834.x] [PMID: 19141166]
[69]
Schmitt, M.; Mengele, K.; Napieralski, R.; Magdolen, V.; Reuning, U.; Gkazepis, A.; Sweep, F.; Brünner, N.; Foekens, J.; Harbeck, N. Clinical utility of level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1. Expert Rev. Mol. Diagn., 2010, 10(8), 1051-1067.
[http://dx.doi.org/10.1586/erm.10.71] [PMID: 21080821]
[http://dx.doi.org/10.1586/erm.10.71] [PMID: 21080821]
[70]
Alessi, M.C.; Juhan-Vague, I. PAI-1 and the metabolic syndrome: links, causes, and consequences. Arterioscler. Thromb. Vasc. Biol., 2006, 26(10), 2200-2207.
[http://dx.doi.org/10.1161/01.ATV.0000242905.41404.68] [PMID: 16931789]
[http://dx.doi.org/10.1161/01.ATV.0000242905.41404.68] [PMID: 16931789]
[71]
O’Reilly, M.S.; Pirie-Shepherd, S.; Lane, W.S.; Folkman, J. Antiangiogenic activity of the cleaved conformation of the serpin antithrombin. Science, 1999, 285(5435), 1926-1928.
[http://dx.doi.org/10.1126/science.285.5435.1926] [PMID: 10489375]
[http://dx.doi.org/10.1126/science.285.5435.1926] [PMID: 10489375]
[72]
Turk, B. Targeting proteases: successes, failures and future prospects. Nat. Rev. Drug Discov., 2006, 5(9), 785-799.
[http://dx.doi.org/10.1038/nrd2092] [PMID: 16955069]
[http://dx.doi.org/10.1038/nrd2092] [PMID: 16955069]
[73]
Danalev, D. Inhibitors of serine proteinases from blood coagulation cascade - view on current developments. Mini Rev. Med. Chem., 2012, 12(8), 721-730.
[http://dx.doi.org/10.2174/138955712801264819] [PMID: 22512557]
[http://dx.doi.org/10.2174/138955712801264819] [PMID: 22512557]
[74]
Brand, B.; Graf, L. [New anticoagulants - direct thrombin inhibitors]. Ther. Umsch., 2012, 69(11), 643-649.
[http://dx.doi.org/10.1024/0040-5930/a000342] [PMID: 23117667]
[http://dx.doi.org/10.1024/0040-5930/a000342] [PMID: 23117667]
[75]
Streif, W.; Ageno, W. Direct thrombin and factor Xa inhibitors in children: a quest for new anticoagulants for children. Wien. Med. Wochenschr., 2011, 161(3-4), 73-79.
[http://dx.doi.org/10.1007/s10354-011-0879-5] [PMID: 21404143]
[http://dx.doi.org/10.1007/s10354-011-0879-5] [PMID: 21404143]
[76]
Gailani, D.; Gruber, A. Factor XI as a therapeutic target. Arterioscler. Thromb. Vasc. Biol., 2016, 36(7), 1316-1322.
[http://dx.doi.org/10.1161/ATVBAHA.116.306925] [PMID: 27174099]
[http://dx.doi.org/10.1161/ATVBAHA.116.306925] [PMID: 27174099]
[77]
Gailani, D.; Renné, T. Intrinsic pathway of coagulation and arterial thrombosis. Arterioscler. Thromb. Vasc. Biol., 2007, 27(12), 2507-2513.
[http://dx.doi.org/10.1161/ATVBAHA.107.155952] [PMID: 17916770]
[http://dx.doi.org/10.1161/ATVBAHA.107.155952] [PMID: 17916770]
[78]
Weitz, J.I. Factor XI and factor XII as targets for new anticoagulants. Thromb. Res., 2016, 141(Suppl. 2), S40-S45.
[http://dx.doi.org/10.1016/S0049-3848(16)30363-2] [PMID: 27207423]
[http://dx.doi.org/10.1016/S0049-3848(16)30363-2] [PMID: 27207423]
[79]
Pal, N.; Kertai, M.D.; Lakshminarasimhachar, A.; Avidan, M.S. Pharmacology and clinical applications of human recombinant antithrombin. Expert Opin. Biol. Ther., 2010, 10(7), 1155-1168.
[http://dx.doi.org/10.1517/14712598.2010.495713] [PMID: 20528611]
[http://dx.doi.org/10.1517/14712598.2010.495713] [PMID: 20528611]
[80]
Mack, G.S.; Marshall, A. Lost in migration. Nat. Biotechnol., 2010, 28(3), 214-229.
[http://dx.doi.org/10.1038/nbt0310-214] [PMID: 20212481]
[http://dx.doi.org/10.1038/nbt0310-214] [PMID: 20212481]
[81]
Schmitt, M.; Harbeck, N.; Brünner, N.; Jänicke, F.; Meisner, C.; Mühlenweg, B.; Jansen, H.; Dorn, J.; Nitz, U.; Kantelhardt, E.J.; Thomssen, C. Cancer therapy trials employing level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1. Expert Rev. Mol. Diagn., 2011, 11(6), 617-634.
[http://dx.doi.org/10.1586/erm.11.47] [PMID: 21745015]
[http://dx.doi.org/10.1586/erm.11.47] [PMID: 21745015]
[82]
Gadek, J.E.; Hosea, S.W.; Gelfand, J.A.; Santaella, M.; Wickerhauser, M.; Triantaphyllopoulos, D.C.; Frank, M.M. Replacement therapy in hereditary angioedema: successful treatment of acute episodes of angioedema with partly purified C1 inhibitor. N. Engl. J. Med., 1980, 302(10), 542-546.
[http://dx.doi.org/10.1056/NEJM198003063021002] [PMID: 7351888]
[http://dx.doi.org/10.1056/NEJM198003063021002] [PMID: 7351888]
[83]
Martello, J.L.; Woytowish, M.R.; Chambers, H. Ecallantide for treatment of acute attacks of hereditary angioedema. Am. J. Health Syst. Pharm., 2012, 69(8), 651-657.
[http://dx.doi.org/10.2146/ajhp110227] [PMID: 22472866]
[http://dx.doi.org/10.2146/ajhp110227] [PMID: 22472866]
[84]
Shakur, H.; Beaumont, D.; Pavord, S.; Gayet-Ageron, A.; Ker, K.; Mousa, H.A. Antifibrinolytic drugs for treating primary postpartum haemorrhage. . Cochrane Database Syst.
Rev., 2018, 2CD012964,
[http://dx.doi.org/10.1002/14651858.CD012964] [PMID: 29462500]
[http://dx.doi.org/10.1002/14651858.CD012964] [PMID: 29462500]
[85]
Lipinski, C.A. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov. Today. Technol., 2004, 1(4), 337-341.
[http://dx.doi.org/10.1016/j.ddtec.2004.11.007] [PMID: 24981612]
[http://dx.doi.org/10.1016/j.ddtec.2004.11.007] [PMID: 24981612]
[86]
Duffy, F.J.; Devocelle, M.; Shields, D.C. Computational approaches to developing short cyclic peptide modulators of protein-protein interactions. Methods Mol. Biol., 2015, 1268, 241-271.
[http://dx.doi.org/10.1007/978-1-4939-2285-7_11] [PMID: 25555728]
[http://dx.doi.org/10.1007/978-1-4939-2285-7_11] [PMID: 25555728]
[87]
Baeriswyl, V.; Heinis, C. Polycyclic peptide therapeutics. Chem.Med.Chem, 2013, 8(3), 377-384.
[http://dx.doi.org/10.1002/cmdc.201200513] [PMID: 23355488]
[http://dx.doi.org/10.1002/cmdc.201200513] [PMID: 23355488]
[88]
Craik, D.J.; Fairlie, D.P.; Liras, S.; Price, D. The future of peptide-based drugs. Chem. Biol. Drug Des., 2013, 81(1), 136-147.
[http://dx.doi.org/10.1111/cbdd.12055] [PMID: 23253135]
[http://dx.doi.org/10.1111/cbdd.12055] [PMID: 23253135]
[89]
Huai, Q.; Mazar, A.P.; Kuo, A.; Parry, G.C.; Shaw, D.E.; Callahan, J.; Li, Y.; Yuan, C.; Bian, C.; Chen, L.; Furie, B.; Furie, B.C.; Cines, D.B.; Huang, M. Structure of human urokinase plasminogen activator in complex with its receptor. Science, 2006, 311(5761), 656-659.
[http://dx.doi.org/10.1126/science.1121143] [PMID: 16456079]
[http://dx.doi.org/10.1126/science.1121143] [PMID: 16456079]
[90]
Bugge, T.H.; Antalis, T.M.; Wu, Q. Type II transmembrane serine proteases. J. Biol. Chem., 2009, 284(35), 23177-23181.
[http://dx.doi.org/10.1074/jbc.R109.021006] [PMID: 19487698]
[http://dx.doi.org/10.1074/jbc.R109.021006] [PMID: 19487698]
[91]
Renné, T.; Sugiyama, A.; Gailani, D.; Jahnen-Dechent, W.; Walter, U.; Müller-Esterl, W. Fine mapping of the H-kininogen binding site in plasma prekallikrein apple domain 2. Int. Immunopharmacol., 2002, 2(13-14), 1867-1873.
[http://dx.doi.org/10.1016/S1567-5769(02)00170-4] [PMID: 12489801]
[http://dx.doi.org/10.1016/S1567-5769(02)00170-4] [PMID: 12489801]
[92]
Lin, Z.; Jiang, L.; Yuan, C.; Jensen, J.K.; Zhang, X.; Luo, Z.; Furie, B.C.; Furie, B.; Andreasen, P.A.; Huang, M. Structural basis for recognition of urokinase-type plasminogen activator by plasminogen activator inhibitor-1. J. Biol. Chem., 2011, 286(9), 7027-7032.
[http://dx.doi.org/10.1074/jbc.M110.204537] [PMID: 21199867]
[http://dx.doi.org/10.1074/jbc.M110.204537] [PMID: 21199867]
[93]
Crippa, M.P. Urokinase-type plasminogen activator. Int. J. Biochem. Cell Biol., 2007, 39(4), 690-694.
[http://dx.doi.org/10.1016/j.biocel.2006.10.008] [PMID: 17118695]
[http://dx.doi.org/10.1016/j.biocel.2006.10.008] [PMID: 17118695]
[94]
Otlewski, J.; Jelen, F.; Zakrzewska, M.; Oleksy, A. The many faces of protease-protein inhibitor interaction. EMBO J., 2005, 24(7), 1303-1310.
[http://dx.doi.org/10.1038/sj.emboj.7600611] [PMID: 15775973]
[http://dx.doi.org/10.1038/sj.emboj.7600611] [PMID: 15775973]
[95]
Perona, J.J.; Craik, C.S. Structural basis of substrate specificity in the serine proteases. Protein Sci., 1995, 4(3), 337-360.
[http://dx.doi.org/10.1002/pro.5560040301] [PMID: 7795518]
[http://dx.doi.org/10.1002/pro.5560040301] [PMID: 7795518]
[96]
Drag, M.; Salvesen, G.S. Emerging principles in protease-based drug discovery. Nat. Rev. Drug Discov., 2010, 9(9), 690-701.
[http://dx.doi.org/10.1038/nrd3053] [PMID: 20811381]
[http://dx.doi.org/10.1038/nrd3053] [PMID: 20811381]
[97]
Coussens, L.M.; Fingleton, B.; Matrisian, L.M. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science, 2002, 295(5564), 2387-2392.
[http://dx.doi.org/10.1126/science.1067100] [PMID: 11923519]
[http://dx.doi.org/10.1126/science.1067100] [PMID: 11923519]
[98]
Setyono-Han, B.; Stürzebecher, J.; Schmalix, W.A.; Muehlenweg, B.; Sieuwerts, A.M.; Timmermans, M.; Magdolen, V.; Schmitt, M.; Klijn, J.G.M.; Foekens, J.A. Suppression of rat breast cancer metastasis and reduction of primary tumour growth by the small synthetic urokinase inhibitor WX-UK1. Thromb. Haemost., 2005, 93(4), 779-786.
[http://dx.doi.org/10.1160/TH04-11-0712] [PMID: 15841327]
[http://dx.doi.org/10.1160/TH04-11-0712] [PMID: 15841327]
[99]
Fergal, J.; Duffy, M.D.; Denis, C. Shields. Computational Peptidology.Peng Zhou, J.H; York, S.N., Ed.; New York, 2015, pp. 241-271.
[http://dx.doi.org/ 10.1007/978-1-4939-2285-7]
[http://dx.doi.org/ 10.1007/978-1-4939-2285-7]
[100]
Xu, P.; Xu, M.; Jiang, L.; Yang, Q.; Luo, Z.; Dauter, Z.; Huang, M.; Andreasen, P.A. Design of specific serine protease inhibitors based on a versatile peptide scaffold: Conversion of a urokinase inhibitor to a plasma kallikrein inhibitor. J. Med. Chem., 2015, 58(22), 8868-8876.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01128] [PMID: 26536069]
[http://dx.doi.org/10.1021/acs.jmedchem.5b01128] [PMID: 26536069]
[101]
Mahatmanto, T. Review seed biopharmaceutical cyclic peptides: From discovery to applications. Biopolymers, 2015, 104(6), 804-814.
[http://dx.doi.org/10.1002/bip.22741] [PMID: 26385189]
[http://dx.doi.org/10.1002/bip.22741] [PMID: 26385189]
[102]
Lesner, A.; Łęgowska, A.; Wysocka, M.; Rolka, K. Sunflower trypsin inhibitor 1 as a molecular scaffold for drug discovery. Curr. Pharm. Des., 2011, 17(38), 4308-4317.
[http://dx.doi.org/10.2174/138161211798999393] [PMID: 22204429]
[http://dx.doi.org/10.2174/138161211798999393] [PMID: 22204429]
[103]
Luckett, S.; Garcia, R.S.; Barker, J.J.; Konarev, A.V.; Shewry, P.R.; Clarke, A.R.; Brady, R.L. High-resolution structure of a potent, cyclic proteinase inhibitor from sunflower seeds. J. Mol. Biol., 1999, 290(2), 525-533.
[http://dx.doi.org/10.1006/jmbi.1999.2891] [PMID: 10390350]
[http://dx.doi.org/10.1006/jmbi.1999.2891] [PMID: 10390350]
[104]
Chen, P.; Rose, J.; Love, R.; Wei, C.H.; Wang, B.C. Reactive sites of an anticarcinogenic Bowman-Birk proteinase inhibitor are similar to other trypsin inhibitors. J. Biol. Chem., 1992, 267(3), 1990-1994.
[PMID: 1730730]
[PMID: 1730730]
[105]
Swedberg, J.E.; Nigon, L.V.; Reid, J.C.; de Veer, S.J.; Walpole, C.M.; Stephens, C.R.; Walsh, T.P.; Takayama, T.K.; Hooper, J.D.; Clements, J.A.; Buckle, A.M.; Harris, J.M. Substrate-guided design of a potent and selective kallikrein-related peptidase inhibitor for kallikrein 4. Chem. Biol., 2009, 16(6), 633-643.
[http://dx.doi.org/10.1016/j.chembiol.2009.05.008] [PMID: 19549601]
[http://dx.doi.org/10.1016/j.chembiol.2009.05.008] [PMID: 19549601]
[106]
de Veer, S.J.; Swedberg, J.E.; Brattsand, M.; Clements, J.A.; Harris, J.M. Exploring the active site binding specificity of kallikrein-related peptidase 5 (KLK5) guides the design of new peptide substrates and inhibitors. Biol. Chem., 2016, 397(12), 1237-1249.
[http://dx.doi.org/10.1515/hsz-2016-0112] [PMID: 26894578]
[http://dx.doi.org/10.1515/hsz-2016-0112] [PMID: 26894578]
[107]
de Veer, S.J.; Swedberg, J.E.; Akcan, M.; Rosengren, K.J.; Brattsand, M.; Craik, D.J.; Harris, J.M. Engineered protease inhibitors based on sunflower trypsin inhibitor-1 (SFTI-1) provide insights into the role of sequence and conformation in Laskowski mechanism inhibition. Biochem. J., 2015, 469(2), 243-253.
[http://dx.doi.org/10.1042/BJ20150412] [PMID: 25981970]
[http://dx.doi.org/10.1042/BJ20150412] [PMID: 25981970]
[108]
de Veer, S.J.; Furio, L.; Swedberg, J.E.; Munro, C.A.; Brattsand, M.; Clements, J.A.; Hovnanian, A.; Harris, J.M. Selective substrates and inhibitors for kallikrein-related peptidase 7 (KLK7) shed light on KLK proteolytic activity in the stratum corneum. J. Invest. Dermatol., 2017, 137(2), 430-439.
[http://dx.doi.org/10.1016/j.jid.2016.09.017] [PMID: 27697464]
[http://dx.doi.org/10.1016/j.jid.2016.09.017] [PMID: 27697464]
[109]
Silvestri, L.; Pagani, A.; Nai, A.; De Domenico, I.; Kaplan, J.; Camaschella, C. The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab., 2008, 8(6), 502-511.
[http://dx.doi.org/10.1016/j.cmet.2008.09.012] [PMID: 18976966]
[http://dx.doi.org/10.1016/j.cmet.2008.09.012] [PMID: 18976966]
[110]
Silvestri, L.; Guillem, F.; Pagani, A.; Nai, A.; Oudin, C.; Silva, M.; Toutain, F.; Kannengiesser, C.; Beaumont, C.; Camaschella, C.; Grandchamp, B. Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with iron-refractory iron deficiency anemia. Blood, 2009, 113(22), 5605-5608.
[http://dx.doi.org/10.1182/blood-2008-12-195594] [PMID: 19357398]
[http://dx.doi.org/10.1182/blood-2008-12-195594] [PMID: 19357398]
[111]
Long, Y.Q.; Lee, S.L.; Lin, C.Y.; Enyedy, I.J.; Wang, S.; Li, P.; Dickson, R.B.; Roller, P.P. Synthesis and evaluation of the sunflower derived trypsin inhibitor as a potent inhibitor of the type II transmembrane serine protease, matriptase. Bioorg. Med. Chem. Lett., 2001, 11(18), 2515-2519.
[http://dx.doi.org/10.1016/S0960-894X(01)00493-0] [PMID: 11549459]
[http://dx.doi.org/10.1016/S0960-894X(01)00493-0] [PMID: 11549459]
[112]
Jiang, S.; Li, P.; Lee, S.L.; Lin, C.Y.; Long, Y.Q.; Johnson, M.D.; Dickson, R.B.; Roller, P.P. Design and synthesis of redox stable analogues of sunflower trypsin inhibitors (SFTI-1) on solid support, potent inhibitors of matriptase. Org. Lett., 2007, 9(1), 9-12.
[http://dx.doi.org/10.1021/ol0621497] [PMID: 17192072]
[http://dx.doi.org/10.1021/ol0621497] [PMID: 17192072]
[113]
Li, P.; Jiang, S.; Lee, S.L.; Lin, C.Y.; Johnson, M.D.; Dickson, R.B.; Michejda, C.J.; Roller, P.P. Design and synthesis of novel and potent inhibitors of the type II transmembrane serine protease, matriptase, based upon the sunflower trypsin inhibitor-1. J. Med. Chem., 2007, 50(24), 5976-5983.
[http://dx.doi.org/10.1021/jm0704898] [PMID: 17985858]
[http://dx.doi.org/10.1021/jm0704898] [PMID: 17985858]
[114]
Yuan, C.; Chen, L.; Meehan, E.J.; Daly, N.; Craik, D.J.; Huang, M.; Ngo, J.C. Structure of catalytic domain of Matriptase in complex with Sunflower trypsin inhibitor-1. BMC Struct. Biol., 2011, 11, 30.
[http://dx.doi.org/10.1186/1472-6807-11-30] [PMID: 21693064]
[http://dx.doi.org/10.1186/1472-6807-11-30] [PMID: 21693064]
[115]
Avrutina, O.; Fittler, H.; Glotzbach, B.; Kolmar, H.; Empting, M. Between two worlds: a comparative study on in vitro and in silico inhibition of trypsin and matriptase by redox-stable SFTI-1 variants at near physiological pH. Org. Biomol. Chem., 2012, 10(38), 7753-7762.
[http://dx.doi.org/10.1039/c2ob26162f] [PMID: 22903577]
[http://dx.doi.org/10.1039/c2ob26162f] [PMID: 22903577]
[116]
Fittler, H.; Avrutina, O.; Glotzbach, B.; Empting, M.; Kolmar, H. Combinatorial tuning of peptidic drug candidates: high-affinity matriptase inhibitors through incremental structure-guided optimization. Org. Biomol. Chem., 2013, 11(11), 1848-1857.
[http://dx.doi.org/10.1039/c3ob27469a] [PMID: 23361403]
[http://dx.doi.org/10.1039/c3ob27469a] [PMID: 23361403]
[117]
Quimbar, P.; Malik, U.; Sommerhoff, C.P.; Kaas, Q.; Chan, L.Y.; Huang, Y.H.; Grundhuber, M.; Dunse, K.; Craik, D.J.; Anderson, M.A.; Daly, N.L. High-affinity cyclic peptide matriptase inhibitors. J. Biol. Chem., 2013, 288(19), 13885-13896.
[http://dx.doi.org/10.1074/jbc.M113.460030] [PMID: 23548907]
[http://dx.doi.org/10.1074/jbc.M113.460030] [PMID: 23548907]
[118]
Gitlin, A.; Dębowski, D.; Karna, N.; Łęgowska, A.; Stirnberg, M.; Gütschow, M.; Rolka, K. Inhibitors of matriptase-2 based on the trypsin inhibitor SFTI-1. Chem.Bio.Chem, 2015, 16(11), 1601-1607.
[http://dx.doi.org/10.1002/cbic.201500200] [PMID: 25999208]
[http://dx.doi.org/10.1002/cbic.201500200] [PMID: 25999208]
[119]
Koivunen, E.; Wang, B.; Dickinson, C.D.; Ruoslahti, E. Peptides in cell adhesion research. Methods Enzymol., 1994, 245, 346-369.
[http://dx.doi.org/10.1016/0076-6879(94)45019-6] [PMID: 7760743]
[http://dx.doi.org/10.1016/0076-6879(94)45019-6] [PMID: 7760743]
[120]
Petersen, H.H.; Hansen, M.; Schousboe, S.L.; Andreasen, P.A. Localization of epitopes for monoclonal antibodies to urokinase-type plasminogen activator: relationship between epitope localization and effects of antibodies on molecular interactions of the enzyme. Eur. J. Biochem., 2001, 268(16), 4430-4439.
[http://dx.doi.org/10.1046/j.1432-1327.2001.02365.x] [PMID: 11502203]
[http://dx.doi.org/10.1046/j.1432-1327.2001.02365.x] [PMID: 11502203]
[121]
Hansen, M.; Wind, T.; Blouse, G.E.; Christensen, A.; Petersen, H.H.; Kjelgaard, S.; Mathiasen, L.; Holtet, T.L.; Andreasen, P.A. A urokinase-type plasminogen activator-inhibiting cyclic peptide with an unusual P2 residue and an extended protease binding surface demonstrates new modalities for enzyme inhibition. J. Biol. Chem., 2005, 280(46), 38424-38437.
[http://dx.doi.org/10.1074/jbc.M505933200] [PMID: 16141208]
[http://dx.doi.org/10.1074/jbc.M505933200] [PMID: 16141208]
[122]
Zhao, G.; Yuan, C.; Wind, T.; Huang, Z.; Andreasen, P.A.; Huang, M. Structural basis of specificity of a peptidyl urokinase inhibitor, upain-1. J. Struct. Biol., 2007, 160(1), 1-10.
[http://dx.doi.org/10.1016/j.jsb.2007.06.003] [PMID: 17692534]
[http://dx.doi.org/10.1016/j.jsb.2007.06.003] [PMID: 17692534]
[123]
Roodbeen, R.; Paaske, B.; Jiang, L.; Jensen, J.K.; Christensen, A.; Nielsen, J.T.; Huang, M.; Mulder, F.A.A.; Nielsen, N.C.; Andreasen, P.A.; Jensen, K.J. Bicyclic peptide inhibitor of urokinase-type plasminogen activator: mode of action. Chem.Bio.Chem, 2013, 14(16), 2179-2188.
[http://dx.doi.org/10.1002/cbic.201300335] [PMID: 24115455]
[http://dx.doi.org/10.1002/cbic.201300335] [PMID: 24115455]
[124]
Jiang, L.; Andersen, L.M.; Andreasen, P.A.; Chen, L.; Huang, M. Insights into the serine protease mechanism based on structural observations of the conversion of a peptidyl serine protease inhibitor to a substrate. Biochim. Biophys. Acta, 2016, 1860(3), 599-606.
[http://dx.doi.org/10.1016/j.bbagen.2015.12.009] [PMID: 26691138]
[http://dx.doi.org/10.1016/j.bbagen.2015.12.009] [PMID: 26691138]
[125]
Andersen, L.M.; Wind, T.; Hansen, H.D.; Andreasen, P.A. A cyclic peptidylic inhibitor of murine urokinase-type plasminogen activator: changing species specificity by substitution of a single residue. Biochem. J., 2008, 412(3), 447-457.
[http://dx.doi.org/10.1042/BJ20071646] [PMID: 18318660]
[http://dx.doi.org/10.1042/BJ20071646] [PMID: 18318660]
[126]
Hosseini, M.; Jiang, L.; Sørensen, H.P.; Jensen, J.K.; Christensen, A.; Fogh, S.; Yuan, C.; Andersen, L.M.; Huang, M.; Andreasen, P.A.; Jensen, K.J. Elucidation of the contribution of active site and exosite interactions to affinity and specificity of peptidylic serine protease inhibitors using non-natural arginine analogs. Mol. Pharmacol., 2011, 80(4), 585-597.
[http://dx.doi.org/10.1124/mol.111.072280] [PMID: 21719463]
[http://dx.doi.org/10.1124/mol.111.072280] [PMID: 21719463]
[127]
Sørensen, H.P.; Xu, P.; Jiang, L.; Kromann-Hansen, T.; Jensen, K.J.; Huang, M.; Andreasen, P.A. Selection of high-affinity peptidic serine protease inhibitors with increased binding entropy from a back-flip library of peptide-protease fusions. J. Mol. Biol., 2015, 427(19), 3110-3122.
[http://dx.doi.org/10.1016/j.jmb.2015.08.005] [PMID: 26281711]
[http://dx.doi.org/10.1016/j.jmb.2015.08.005] [PMID: 26281711]
[128]
Heinis, C.; Rutherford, T.; Freund, S.; Winter, G. Phage-encoded combinatorial chemical libraries based on bicyclic peptides. Nat. Chem. Biol., 2009, 5(7), 502-507.
[http://dx.doi.org/10.1038/nchembio.184] [PMID: 19483697]
[http://dx.doi.org/10.1038/nchembio.184] [PMID: 19483697]
[129]
Angelini, A.; Cendron, L.; Chen, S.; Touati, J.; Winter, G.; Zanotti, G.; Heinis, C. Bicyclic peptide inhibitor reveals large contact interface with a protease target. ACS Chem. Biol., 2012, 7(5), 817-821.
[http://dx.doi.org/10.1021/cb200478t] [PMID: 22304751]
[http://dx.doi.org/10.1021/cb200478t] [PMID: 22304751]
[130]
Baeriswyl, V.; Calzavarini, S.; Gerschheimer, C.; Diderich, P.; Angelillo-Scherrer, A.; Heinis, C. Development of a selective peptide macrocycle inhibitor of coagulation factor XII toward the generation of a safe antithrombotic therapy. J. Med. Chem., 2013, 56(9), 3742-3746.
[http://dx.doi.org/10.1021/jm400236j] [PMID: 23586812]
[http://dx.doi.org/10.1021/jm400236j] [PMID: 23586812]
[131]
Baeriswyl, V.; Rapley, H.; Pollaro, L.; Stace, C.; Teufel, D.; Walker, E.; Chen, S.; Winter, G.; Tite, J.; Heinis, C. Bicyclic peptides with optimized ring size inhibit human plasma kallikrein and its orthologues while sparing paralogous proteases. Chem.Med.Chem, 2012, 7(7), 1173-1176.
[http://dx.doi.org/10.1002/cmdc.201200071] [PMID: 22492508]
[http://dx.doi.org/10.1002/cmdc.201200071] [PMID: 22492508]
[132]
Chen, S.; Rentero Rebollo, I.; Buth, S.A.; Morales-Sanfrutos, J.; Touati, J.; Leiman, P.G.; Heinis, C. Bicyclic peptide ligands pulled out of cysteine-rich peptide libraries. J. Am. Chem. Soc., 2013, 135(17), 6562-6569.
[http://dx.doi.org/10.1021/ja400461h] [PMID: 23560397]
[http://dx.doi.org/10.1021/ja400461h] [PMID: 23560397]
[133]
Chen, S.; Gfeller, D.; Buth, S.A.; Michielin, O.; Leiman, P.G.; Heinis, C. Improving binding affinity and stability of peptide ligands by substituting glycines with D-amino acids. Chem.Bio.Chem, 2013, 14(11), 1316-1322.
[http://dx.doi.org/10.1002/cbic.201300228] [PMID: 23828687]
[http://dx.doi.org/10.1002/cbic.201300228] [PMID: 23828687]
[134]
Chen, S.; Morales-Sanfrutos, J.; Angelini, A.; Cutting, B.; Heinis, C. Structurally diverse cyclisation linkers impose different backbone conformations in bicyclic peptides. Chem.Bio.Chem, 2012, 13(7), 1032-1038.
[http://dx.doi.org/10.1002/cbic.201200049] [PMID: 22492661]
[http://dx.doi.org/10.1002/cbic.201200049] [PMID: 22492661]
[135]
Chen, S.; Bertoldo, D.; Angelini, A.; Pojer, F.; Heinis, C. Peptide ligands stabilized by small molecules. Angew. Chem. Int. Ed. Engl., 2014, 53(6), 1602-1606.
[http://dx.doi.org/10.1002/anie.201309459] [PMID: 24453110]
[http://dx.doi.org/10.1002/anie.201309459] [PMID: 24453110]
[136]
Chen, S.; Gopalakrishnan, R.; Schaer, T.; Marger, F.; Hovius, R.; Bertrand, D.; Pojer, F.; Heinis, C. Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides. Nat. Chem., 2014, 6(11), 1009-1016.
[http://dx.doi.org/10.1038/nchem.2043] [PMID: 25343607]
[http://dx.doi.org/10.1038/nchem.2043] [PMID: 25343607]
[137]
Wilbs, J.; Middendorp, S.J.; Heinis, C. Improving the binding affinity of in-vitro-evolved cyclic peptides by inserting atoms into the macrocycle backbone. Chem.Bio.Chem, 2016, 17(24), 2299-2303.
[http://dx.doi.org/10.1002/cbic.201600336] [PMID: 27862752]
[http://dx.doi.org/10.1002/cbic.201600336] [PMID: 27862752]
[138]
Werle, M.; Bernkop-Schnürch, A. Strategies to improve plasma half life time of peptide and protein drugs. Amino Acids, 2006, 30(4), 351-367.
[http://dx.doi.org/10.1007/s00726-005-0289-3] [PMID: 16622600]
[http://dx.doi.org/10.1007/s00726-005-0289-3] [PMID: 16622600]
[139]
Angelini, A.; Diderich, P.; Morales-Sanfrutos, J.; Thurnheer, S.; Hacker, D.; Menin, L.; Heinis, C. Chemical macrocyclization of peptides fused to antibody Fc fragments. Bioconjug. Chem., 2012, 23(9), 1856-1863.
[http://dx.doi.org/10.1021/bc300184m] [PMID: 22812498]
[http://dx.doi.org/10.1021/bc300184m] [PMID: 22812498]
[140]
Pollaro, L.; Raghunathan, S.; Morales-Sanfrutos, J.; Angelini, A.; Kontos, S.; Heinis, C. Bicyclic peptides conjugated to an albumin-binding tag diffuse efficiently into solid tumors. Mol. Cancer Ther., 2015, 14(1), 151-161.
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0534] [PMID: 25381263]
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0534] [PMID: 25381263]
[141]
Kawada, M.; Umezawa, K. Suppression of in vitro invasion of human fibrosarcoma cells by a leupeptin analogue inhibiting the urokinase-plasmin system. Biochem. Biophys. Res. Commun., 1995, 209(1), 25-30.
[http://dx.doi.org/10.1006/bbrc.1995.1465] [PMID: 7726842]
[http://dx.doi.org/10.1006/bbrc.1995.1465] [PMID: 7726842]
[142]
Swedberg, J.E.; Harris, J.M. Plasmin substrate binding site cooperativity guides the design of potent peptide aldehyde inhibitors. Biochemistry, 2011, 50(39), 8454-8462.
[http://dx.doi.org/10.1021/bi201203y] [PMID: 21877690]
[http://dx.doi.org/10.1021/bi201203y] [PMID: 21877690]
[143]
Sommer, N.; Tackenberg, B.; Hohlfeld, R. The immunopathogenesis of myasthenia gravis. Handb. Clin. Neurol., 2008, 91, 169-212.
[http://dx.doi.org/10.1016/S0072-9752(07)01505-9] [PMID: 18631843]
[http://dx.doi.org/10.1016/S0072-9752(07)01505-9] [PMID: 18631843]
[144]
Giroux, R. Cyclosporine. Chem. Eng. News, 2005, 83(25), 56-56.
[http://dx.doi.org/10.1021/cen-v083n025.p056]
[http://dx.doi.org/10.1021/cen-v083n025.p056]
[145]
Warkentin, T.E.; Greinacher, A.; Koster, A. Bivalirudin. Thromb. Haemost., 2008, 99(5), 830-839.
[PMID: 18449412]
[PMID: 18449412]
[146]
Joseph, L.; Casanegra, A.I.; Dhariwal, M.; Smith, M.A.; Raju, M.G.; Militello, M.A.; Gomes, M.P.; Gornik, H.L.; Bartholomew, J.R. Bivalirudin for the treatment of patients with confirmed or suspected heparin-induced thrombocytopenia. J. Thromb. Haemost., 2014, 12(7), 1044-1053.
[http://dx.doi.org/10.1111/jth.12592] [PMID: 24766902]
[http://dx.doi.org/10.1111/jth.12592] [PMID: 24766902]
[147]
Pollaro, L.; Heinis, C. Strategies to prolong the plasma residence time of peptide drugs. Med.Chem.Comm, 2010, 1(5), 319-324.
[http://dx.doi.org/10.1039/C0MD00111B]
[http://dx.doi.org/10.1039/C0MD00111B]
[148]
Pasut, G.; Guiotto, A.; Veronese, F. Protein, peptide and non-peptide drug PEGylation for therapeutic application. Expert Opin. Ther. Pat., 2004, 14(6), 859-894.
[http://dx.doi.org/10.1517/13543776.14.6.859]
[http://dx.doi.org/10.1517/13543776.14.6.859]
[149]
Colley, K.J.; Kitajima, K.; Sato, C. Polysialic acid: biosynthesis, novel functions and applications. Crit. Rev. Biochem. Mol. Biol., 2014, 49(6), 498-532.
[http://dx.doi.org/10.3109/10409238.2014.976606] [PMID: 25373518]
[http://dx.doi.org/10.3109/10409238.2014.976606] [PMID: 25373518]
[150]
Paleos, C.M.; Sideratou, Z.; Tsiourvas, D. Drug delivery systems based on hydroxyethyl starch. Bioconjug. Chem., 2017, 28(6), 1611-1624.
[http://dx.doi.org/10.1021/acs.bioconjchem.7b00186] [PMID: 28431209]
[http://dx.doi.org/10.1021/acs.bioconjchem.7b00186] [PMID: 28431209]
[151]
Li, R.; Zheng, K.; Hu, P.; Chen, Z.; Zhou, S.; Chen, J.; Yuan, C.; Chen, S.; Zheng, W.; Ma, E.; Zhang, F.; Xue, J.; Chen, X.; Huang, M. A novel tumor targeting drug carrier for optical imaging and therapy. Theranostics, 2014, 4(6), 642-659.
[http://dx.doi.org/10.7150/thno.8527] [PMID: 24723985]
[http://dx.doi.org/10.7150/thno.8527] [PMID: 24723985]
[152]
Zhou, X.; Zheng, K.; Li, R.; Chen, Z.; Yuan, C.; Hu, P.; Chen, J.; Xue, J.; Huang, M. A drug carrier targeting murine uPAR for photodynamic therapy and tumor imaging. Acta Biomater., 2015, 23, 116-126.
[http://dx.doi.org/10.1016/j.actbio.2015.05.017] [PMID: 26004218]
[http://dx.doi.org/10.1016/j.actbio.2015.05.017] [PMID: 26004218]
[153]
Peng, S.; Xue, G.; Gong, L.; Fang, C.; Chen, J.; Yuan, C.; Chen, Z.; Yao, L.; Furie, B.; Huang, M. A long-acting PAI-1 inhibitor reduces thrombus formation. Thromb. Haemost., 2017, 117(7), 1338-1347.
[http://dx.doi.org/10.1160/TH16-11-0891] [PMID: 28405670]
[http://dx.doi.org/10.1160/TH16-11-0891] [PMID: 28405670]
[154]
Gong, L.; Proulle, V.; Fang, C.; Hong, Z.; Lin, Z.; Liu, M.; Xue, G.; Yuan, C.; Lin, L.; Furie, B.; Flaumenhaft, R.; Andreasen, P.; Furie, B.; Huang, M. A specific plasminogen activator inhibitor-1 antagonist derived from inactivated urokinase. J. Cell. Mol. Med., 2016, 20(10), 1851-1860.
[http://dx.doi.org/10.1111/jcmm.12875] [PMID: 27197780]
[http://dx.doi.org/10.1111/jcmm.12875] [PMID: 27197780]
[155]
Menear, K. Progress towards the discovery of orally active thrombin inhibitors. Curr. Med. Chem., 1998, 5(6), 457-468.
[PMID: 9873110]
[PMID: 9873110]
[156]
Liang, G.; Bowen, J.P. Development of trypsin-like serine protease inhibitors as therapeutic agents: Opportunities, challenges, and their unique structure-based rationales. Curr. Top. Med. Chem., 2016, 16(13), 1506-1529.
[http://dx.doi.org/10.2174/1568026615666150915121447] [PMID: 26369819]
[http://dx.doi.org/10.2174/1568026615666150915121447] [PMID: 26369819]
[157]
Xue, G.; Gong, L.; Yuan, C.; Xu, M.; Wang, X.; Jiang, L.; Huang, M. A structural mechanism of flavonoids in inhibiting serine proteases. Food Funct., 2017, 8(7), 2437-2443.
[http://dx.doi.org/10.1039/C6FO01825D] [PMID: 28644504]
[http://dx.doi.org/10.1039/C6FO01825D] [PMID: 28644504]
[158]
Jiang, L.; Zhang, X.; Zhou, Y.; Chen, Y.; Luo, Z.; Li, J.; Yuan, C.; Huang, M. Halogen bonding for the design of inhibitors by targeting the S1 pocket of serine proteases. Rsc Adv., 2018, 8(49), 28189-28197.
[http://dx.doi.org/10.1039/C8RA03145B]
[http://dx.doi.org/10.1039/C8RA03145B]
[159]
Boos, C.J.; Nam, M.; Camm, A.J. Novel oral anticoagulants and stroke prevention in atrial fibrillation and chronic heart failure. Heart Fail. Rev., 2014, 19(3), 391-401.
[http://dx.doi.org/10.1007/s10741-013-9398-3] [PMID: 23797696]
[http://dx.doi.org/10.1007/s10741-013-9398-3] [PMID: 23797696]
[160]
Pollack, C.V., Jr; Reilly, P.A.; Eikelboom, J.; Glund, S.; Verhamme, P.; Bernstein, R.A.; Dubiel, R.; Huisman, M.V.; Hylek, E.M.; Kamphuisen, P.W.; Kreuzer, J.; Levy, J.H.; Sellke, F.W.; Stangier, J.; Steiner, T.; Wang, B.; Kam, C.W.; Weitz, J.I. Idarucizumab for dabigatran reversal. N. Engl. J. Med., 2015, 373(6), 511-520.
[http://dx.doi.org/10.1056/NEJMoa1502000] [PMID: 26095746]
[http://dx.doi.org/10.1056/NEJMoa1502000] [PMID: 26095746]
[161]
Brown, N.J. Therapeutic potential of plasminogen activator inhibitor-1 inhibitors. Ther. Adv. Cardiovasc. Dis., 2010, 4(5), 315-324.
[http://dx.doi.org/10.1177/1753944710379126] [PMID: 20660535]
[http://dx.doi.org/10.1177/1753944710379126] [PMID: 20660535]
[162]
Korsinczky, M.L.; Schirra, H.J.; Rosengren, K.J.; West, J.; Condie, B.A.; Otvos, L.; Anderson, M.A.; Craik, D.J. Solution structures by 1H NMR of the novel cyclic trypsin inhibitor SFTI-1 from sunflower seeds and an acyclic permutant. J. Mol. Biol., 2001, 311(3), 579-591.
[http://dx.doi.org/10.1006/jmbi.2001.4887] [PMID: 11493011]
[http://dx.doi.org/10.1006/jmbi.2001.4887] [PMID: 11493011]
[163]
Jiang, L.; Svane, A.S.P.; Sørensen, H.P.; Jensen, J.K.; Hosseini, M.; Chen, Z.; Weydert, C.; Nielsen, J.T.; Christensen, A.; Yuan, C.; Jensen, K.J.; Nielsen, N.C.; Malmendal, A.; Huang, M.; Andreasen, P.A. The binding mechanism of a peptidic cyclic serine protease inhibitor. J. Mol. Biol., 2011, 412(2), 235-250.
[http://dx.doi.org/10.1016/j.jmb.2011.07.028] [PMID: 21802428]
[http://dx.doi.org/10.1016/j.jmb.2011.07.028] [PMID: 21802428]
Article Metrics
![Wayfinder Image](/images/wayfinder.jpg)