Selective Inhibitors of Plasmepsin II of Plasmodium falciparum on the Basis of Pepstatin

被引：1

作者：

Rumsh, L. D. ^{[1
]}

Mikhailova, A. G. ^{[1
]}

Mikhura, I. V. ^{[1
]}

Prudchenko, I. A. ^{[1
]}

Chikin, L. D. ^{[1
]}

Mikhaleva, I. I. ^{[1
]}

Kaliberda, E. N. ^{[1
]}

Dergousova, N. I. ^{[1
]}

Mel'nikov, E. E. ^{[1
]}

Formanovskii, A. A. ^{[1
]}

机构：

[1] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia

来源：

RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY | 2008年 / 34卷 / 06期

关键词：

malaria; proteases; inhibitors; plasmepsin II; Plasmodium falciparum;

D O I：

10.1134/S1068162008060034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A number of new inhibitors of plasmepsin II (PlmII) Plasmodium falciparum, which was one of the key factors of survival of malarial parasite, was synthesized. The inhibitors were analogues of pepstatin with different substitutions for the alanine residue. Effects of the inhibitors on human PlmII and cathepsin D were studied. Inhibition of PlmII by the substrate was found. This discovery required modification of the Henderson method for determination of inhibition constants. Two synthesized inhibitors were shown to exhibit a pronounced selectivity to PlmII (K-i = 5.5 and 5 nM) in comparison with that of cathepsin D (K-i = 230 and 3000 nM, respectively).

引用

页码：660 / 667

页数：8

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