Plasmodium falciparum plasmepsins

Inhibitors for proteases plasmepsin I and II of the malaria parasite Plasmodium falciparum, with a good plasmepsin/human protease cathepsin D selectivity, have been identified via library construction involving rapid microwave-accelerated Suzuki reactions [57]. The phenyl ring of the biphenyl unit in the lead compound M-((lS)-l- [((lS,2S)-3- [(lS)-2-amino-l-(4-phenyl-benzyl)-2-oxoethyl]amino -2-hydroxy-l-phenoxypropyl)amino]carbonyl -2-methylpropyl)pyridine-2-carboxamide has been altered by performing Suzuki reactions on N-((lS)-l- [((lS,2S)-3- [(lS)-2-amino-l-(4-bromobenzyl)-2-oxoethyl]amino -2-hydroxy-l-phenoxypropyl)amino]carbonyl -2-methyl-propyl)pyridine-2-carboxamide (Scheme 37). In particular, a 2-benzofuryl moiety proved to be interesting since a Ki value of 13 nM for plasmepsin I and... 

Noteberg, D., Hamelink, E., Hulten, J., Wahlgren, M., Vrang, L. etal, Design and synthesis of Plasmepsin I and Plasmepsin Ii inhibitors with activity in Plasmodium Falciparum-infected cultured human erythrocytes,... 

Bonilla, J. A., Bonilla, T. D., Yowell, C. A., Fujioka, H., and Dame, J. B. (2007a). Critical roles for the digestive vacuole plasmepsins of Plasmodium falciparum in vacuolar function. Mol. Microbiol. 65, 64—75. 

Guruprasad L, Tanneeru K, Guruptasad K. Struetural rationale for the recognition of arginine at P3 in PEXEL motif containing proteins of Plasmodium falciparum by plasmepsin V. Protein Pept Lett. 2011 18 634-41. 

Plasmepsin 2 Plasmodium falciparum No data M, E, E, E Recombinant expression... 

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