Targeting the dimerization interface of HIV-1 protease: Inhibition with cross-linked interfacial peptides

被引：108

作者：

Zutshi, R ^{[1
]}

Franciskovich, J ^{[1
]}

Shultz, M ^{[1
]}

Schweitzer, B ^{[1
]}

Bishop, P ^{[1
]}

Wilson, M ^{[1
]}

Chmielewski, J ^{[1
]}

机构：

[1] PURDUE UNIV,DEPT CHEM,W LAFAYETTE,IN 47907

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 1997年 / 119卷 / 21期

关键词：

D O I：

10.1021/ja962496j

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Agents have been designed and synthesized which target the dimerization interface of HIV-1 protease. These agents, which contain cross-linked peptides from the N- and C-termini of the protease, both inhibit HIV-1 protease activity and decrease the amount of protease dimer in solution as measured by size exclusion chromatography, protein crosslinking, and protease fluorescence studies. Additionally we have shown that active site-targeted agents inhibit HIV-1 protease activity but have little effect on protease dimerization. These data support the claim that inhibition with the crosslinked agents is based on a decrease in the amount of protease homodimer in solution which in turn is responsible for a decrease in the activity of the protease.

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页码：4841 / 4845

页数：5

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