SUBSTITUTION OF PROLINE WITH PIPECOLIC ACID AT THE SCISSILE BOND CONVERTS A PEPTIDE SUBSTRATE OF HIV PROTEINASE INTO A SELECTIVE INHIBITOR

被引：80

作者：

COPELAND, TD

WONDRAK, EM

TOZSER, J

ROBERTS, MM

OROSZLAN, S

机构：

[1] Laboratory of Molecular Virology and Carcinogenesis, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center P.O., Frederick, MD 21701, Box B

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1990年 / 169卷 / 01期

关键词：

D O I：

10.1016/0006-291X(90)91469-9

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：

The nonapeptide H-Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln-NH2 containing the retroviral Tyr-Pro cleavage site is a good substrate for the proteinase of human immunodeficiency viruses but it is not readily hydrolyzed by other nonviral proteinases including the structurally related pepsin-like aspartic proteinases. Replacing the Pro by L-pipecolic acid (2-piperidinecarboxylic acid) converted the substrate into an effective inhibitor of HIV-1 and HIV-2 proteinases with IC50 of ∼ 1 μM. This compound showed a high degree of selectivity in that it did not inhibit cathepsin D and renin. © 1990.

引用

页码：310 / 314

页数：5

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