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Title: Design of HIV Protease Inhibitors Based on Inorganic Polyhedral Metallacarboranes

HIV protease (HIV PR) is a primary target for anti-HIV drug design. We have previously identified and characterized substituted metallacarboranes as a new class of HIV protease inhibitors. In a structure-guided drug design effort, we connected the two cobalt bis(dicarbollide) clusters with a linker to substituted ammonium group and obtained a set of compounds based on a lead formula [H{sub 2}N-(8-(C{sub 2}H{sub 4}O){sub 2}-1,2-C{sub 2}B{sub 9}H{sub 10})(1',2'-C{sub 2}B{sub 9}H{sub 11})-3,3'-Co){sub 2}]Na. We explored inhibition properties of these compounds with various substitutions, determined the HIV PR:inhibitor crystal structure, and computationally explored the conformational space of the linker. Our results prove the capacity of linker-substituted dual-cage cobalt bis(dicarbollides) as lead compounds for design of more potent inhibitors of HIV PR.
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Publication Date:
OSTI Identifier:
1006094
Resource Type:
Journal Article
Resource Relation:
Journal Name: J. Med. Chem.; Journal Volume: 52; Journal Issue: (22) ; 11, 2009
Research Org:
Argonne National Laboratory (ANL)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
ENGLISH
Subject:
36 MATERIALS SCIENCE; AIDS VIRUS; CAPACITY; COBALT; CRYSTAL STRUCTURE; DESIGN; LEAD COMPOUNDS; TARGETS