[Selective inhibitors of plasmepsin II from Plasmodium falciparum based on pepstatin].
A number of new inhibitors of plasmepsin II (PlmII) from Plasmodium falciparum, one of the key factors of malarial parasite survival, were synthesized. The inhibitors are analogues of pepstatin with various variants of Ala residue substitutions. Effects of the inhibitors on human PlmII and cathepsin D were studied. Inhibition of PlmII by the substrate was found, which required the use of the modified Henderson method for the 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 cathepsin D (K(i) = 230 and 3000 nM, respectively).
Rumsh
L D
LD
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997 Russia. rumsh@enzyme.siobc.ras.ru
Mikhaĭlova
A G
AG
Mikhura
I V
IV
Prudchenko
I A
IA
Chikin
L D
LD
Mikhaleva
I I
II
Kaliberda
E N
EN
Dergousova
N I
NI
Mel'nikov
E E
EE
Formanovskiĭ
A A
AA
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002402:Cathepsin D / Q000037:antagonists & inhibitors / Q000737:chemistry; D006801:Humans; D010436:Pepstatins / Q000737:chemistry; D010963:Plasmodium falciparum / Q000201:enzymology*; D011480:Protease Inhibitors / Q000737:chemistry*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry
D010436:Pepstatins; D011480:Protease Inhibitors; D015800:Protozoan Proteins; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II; C533922:CTSD protein, human; D002402:Cathepsin D; C031375:pepstatin