Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum.

Abstract

The malaria parasite Plasmodium falciparum employs two metallo-aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure-activity relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.

• Authors: Komagal Kannan Sivaraman, Alessandro Paiardini, Marcin Sieńczyk, Chiara Ruggeri, Christine A Oellig, John P Dalton, Peter J Scammells, Marcin Drag, Sheena McGowan
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 56 Issue 12 Pg. 5213-7 (Jun 27 2013) ISSN: 1520-4804 [Electronic] United States
• PMID: 23713488 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Phosphorous Acids
• phosphonic acid
• Arginine
• CD13 Antigens

Topics

• Arginine (chemistry)
• Biomimetic Materials (chemical synthesis, chemistry, pharmacology)
• CD13 Antigens (antagonists & inhibitors, chemistry)
• Catalytic Domain
• Chemistry Techniques, Synthetic
• Enzyme Inhibitors (chemical synthesis, chemistry, pharmacology)
• Models, Molecular
• Phosphorous Acids (chemistry)
• Plasmodium falciparum (enzymology)
• Structure-Activity Relationship