![conference banner](/images/conference-banner.jpeg)
Abstract
One of the greatest challenges in fighting cancer is cell targeting and biomarker selection. The Atypical Chemokine Receptor ACKR3/CXCR7 is expressed on many cancer cell types, including breast cancer and glioblastoma, and binds the endogenous ligands SDF1/CXCL12 and ITAC/CXCL11. A 20 amino acid region of the ACKR3/CXCR7 N-terminus was synthesized and targeted with the NEB PhD™-7 Phage Display Peptide Library. Twenty-nine phages were isolated and heptapeptide inserts sequenced; of these, 23 sequences were unique. A 3D molecular model was created for the ACKR3/CXCR7 N-terminus by mutating the corresponding region of the crystal structure of CXCR4 with bound SDF1/CXCL12. A ClustalW alignment was performed on each peptide sequence using the entire SDF1/CXCL12 sequence as the template. The 23-peptide sequences showed similarity to three distinct regions of the SDF1/CXCL12 molecule. A 3D molecular model was made for each of the phage peptide inserts to visually identify potential areas of steric interference of peptides that simulated CXCL12 regions not in contact with the receptor’s Nterminus. An ELISA analysis of the relative binding affinity between the peptides identified 9 peptides with statistically significant results. The candidate pool of 9 peptides was further reduced to 3 peptides based on their affinity for the targeted N-terminus region peptide versus no target peptide present or a scrambled negative control peptide. The results clearly show the Phage Display protocol can be used to target a synthesized region of the ACKR3/CXCR7 N-terminus. The 3 peptides chosen, P20, P3, and P9, will be the basis for further targeting studies.
Keywords: Atypical chemokine receptor, Glioblastoma, Phage Display, Targeted therapy.
Current Topics in Medicinal Chemistry
Title:Targeting the Atypical Chemokine Receptor ACKR3/CXCR7: Phase 1 - Phage Display Peptide Identification and Characterization
Volume: 16 Issue: 13
Author(s): R.D. Vestal, D.R. LaJeunesse and E.W. Taylor
Affiliation:
Keywords: Atypical chemokine receptor, Glioblastoma, Phage Display, Targeted therapy.
Abstract: One of the greatest challenges in fighting cancer is cell targeting and biomarker selection. The Atypical Chemokine Receptor ACKR3/CXCR7 is expressed on many cancer cell types, including breast cancer and glioblastoma, and binds the endogenous ligands SDF1/CXCL12 and ITAC/CXCL11. A 20 amino acid region of the ACKR3/CXCR7 N-terminus was synthesized and targeted with the NEB PhD™-7 Phage Display Peptide Library. Twenty-nine phages were isolated and heptapeptide inserts sequenced; of these, 23 sequences were unique. A 3D molecular model was created for the ACKR3/CXCR7 N-terminus by mutating the corresponding region of the crystal structure of CXCR4 with bound SDF1/CXCL12. A ClustalW alignment was performed on each peptide sequence using the entire SDF1/CXCL12 sequence as the template. The 23-peptide sequences showed similarity to three distinct regions of the SDF1/CXCL12 molecule. A 3D molecular model was made for each of the phage peptide inserts to visually identify potential areas of steric interference of peptides that simulated CXCL12 regions not in contact with the receptor’s Nterminus. An ELISA analysis of the relative binding affinity between the peptides identified 9 peptides with statistically significant results. The candidate pool of 9 peptides was further reduced to 3 peptides based on their affinity for the targeted N-terminus region peptide versus no target peptide present or a scrambled negative control peptide. The results clearly show the Phage Display protocol can be used to target a synthesized region of the ACKR3/CXCR7 N-terminus. The 3 peptides chosen, P20, P3, and P9, will be the basis for further targeting studies.
Export Options
About this article
Cite this article as:
Vestal R.D., LaJeunesse D.R. and Taylor E.W., Targeting the Atypical Chemokine Receptor ACKR3/CXCR7: Phase 1 - Phage Display Peptide Identification and Characterization, Current Topics in Medicinal Chemistry 2016; 16 (13) . https://dx.doi.org/10.2174/1568026615666150915120037
DOI https://dx.doi.org/10.2174/1568026615666150915120037 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Adaptogens—History and Future Perspectives
Adaptogens are pharmacologically active compounds or plant extracts that are associated with the ability to enhance the body’s stability against stress. The intake of adaptogens is associated not only with a better ability to adapt to stress and maintain or normalise metabolic functions but also with better mental and physical ...read more
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
![Wayfinder Image](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Radiolabeled Peptide Probes for Liver Cancer Imaging
Current Medicinal Chemistry Congenital Choledochal Malformation – Current Concepts and Classification
Current Pediatric Reviews Astrocytes as a 5-HT2B-Mediated SERT-Independent SSRI Target, Slowly Altering Depression-Associated Genes and Function
Current Signal Transduction Therapy The Function of the Selective Inhibitors of Cycloxygenase 2
Mini-Reviews in Medicinal Chemistry Inflammation-Mediating Proteases: Structure, Function in (Patho) Physiology and Inhibition
Protein & Peptide Letters Inhibition of Aurora A Kinase by Alisertib Induces Autophagy and Cell Cycle Arrest and Increases Chemosensitivity in Human Hepatocellular Carcinoma HepG2 Cells
Current Cancer Drug Targets Rho Kinase Inhibitors: Potential Treatments for Diabetes and Diabetic Complications
Current Pharmaceutical Design Drug Repurposing in Oncology: Current Evidence and Future Direction
Current Medicinal Chemistry Interplay between DNA Methyltransferase 1 and microRNAs During Tumorigenesis
Current Drug Targets The Nuclear Orphan Receptor NR4A1 and NR4A3 as Tumor Suppressors in Hematologic Neoplasms
Current Drug Targets Insight into Tumor Hypoxia: Radionuclide-based Biomarker as Diagnostic Tools
Current Topics in Medicinal Chemistry PET and SPECT Imaging of Tumor Biology: New Approaches Towards Oncology Drug Discovery and Development
Current Computer-Aided Drug Design NADPH Oxidases NOXs and DUOXs as Putative Targets for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Synthesis, Characterization and Evaluation of 1,3-Bisindolyl-2-Propen-1- One Derivatives as Potent Anti-Breast Cancer Agents
Current Bioactive Compounds Benzimidazole: A Multifacted Nucelus for Anticancer Agents
Current Organic Chemistry New Features in the Treatment of Androgen-Independent Prostate Cancer
Current Pharmaceutical Design Potential of Plant-Derived Natural Products in the Treatment of Leukemia and Lymphoma
Current Drug Targets Cell-Penetrating Peptide-Mediated Topical Delivery of Biomacromolecular Drugs
Current Pharmaceutical Biotechnology MIIP, a Cytoskeleton Regulator that Blocks Cell Migration and Invasion, Delays Mitosis, and Suppresses Tumorogenesis
Current Protein & Peptide Science 4-Anilinoquinazoline Derivatives with Epidermal Growth Factor Receptor Inhibitor Activity
Anti-Cancer Agents in Medicinal Chemistry