Plasmodium falciparum M1-Aminopeptidase: A Promising Target for the Development of Antimalarials

Author(s): Jorge Gonzalez-Bacerio, Rafael Fando, Alberto del Monte-Martinez, Jean-Louis Charli and Maria de los A. Chávez

Volume 15, Issue 12, 2014

Page: [1144 - 1165] Pages: 22

DOI: 10.2174/1389450115666141024115641

Price: $65

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Abstract

Malaria is a devastating human parasitic disease that receives enhanced attention due to the emergence of resistance to traditional drugs. Thus, the search for new molecular targets is a major goal. PfAM1 is an aminopeptidase from Plasmodium falciparum, William H. Welch 1897, belonging to the M1 family of metalloproteases, which is a promising target of inhibitors to block the intra-erythrocytic stages of the parasite. Since its identification in 1998, many efforts have been done to validate PfAM1 as an appropriate target of antimalarials. The present work is a critical review of the main structural, functional and kinetic characteristics of PfAM1, as well as a summary of the effects of key inhibitors at molecular and cellular levels. The systematization of experimental results should contribute to a better understanding of the properties of PfAM1 as a target of antimalarials and promote research projects focused on the development of PfAM1 inhibitors.

Keywords: Antimalarials, growth inhibition, M1 family, metallo-aminopeptidases, Plasmodium falciparum, protease inhibitors.


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