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
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.
引用
收藏
页码:4841 / 4845
页数:5
相关论文
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