SUBSTITUTIONS AT THE P2' SITE OF GAG P17-P24 AFFECT CLEAVAGE EFFICIENCY BY HIV-1 PROTEASE

被引：39

作者：

MARGOLIN, N ^{[1
]}

HEATH, W ^{[1
]}

OSBORNE, E ^{[1
]}

LAI, M ^{[1
]}

VLAHOS, C ^{[1
]}

机构：

[1] ELI LILLY INT CORP,LILLY RES LAB,BIOCHEM RES,INDIANAPOLIS,IN 46285

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1990年 / 167卷 / 02期

关键词：

D O I：

10.1016/0006-291X(90)92060-D

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：

Heptapeptide substrates containing a single amino acid substitution at the p2′ position of the gag p17-p24 junction (S-Q-N-Y-P-X-V where X = G, A, L, I, F, and W) were compared as substrates for HIV-1 protease. Binding of the Ile-, Leu-, and Ala- containing peptides was about equal although hydrolysis was 20-fold lower for the Ala and Leu peptides compared to Ile. Insertion of Gly or Phe at the p2′ position resulted in significantly lower cleavage of the peptide while a Trp-containing peptide was not cleaved. These data suggest that a relatively small hydrophobic amino acid is important for hydrolysis and binding at this site. Structure-activity studies such as those described here may be useful in the design of specific inhibitors for HIV-1 protease. © 1990.

引用

页码：554 / 560

页数：7

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