Design of HIV protease inhibitors based on inorganic polyhedral metallacarboranes
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19874035
DOI
10.1021/jm9011388
Knihovny.cz E-resources
- MeSH
- Electrons MeSH
- HIV-1 drug effects enzymology MeSH
- HIV Protease chemistry metabolism MeSH
- HIV Protease Inhibitors chemical synthesis chemistry metabolism pharmacology MeSH
- Cobalt chemistry MeSH
- Crystallography, X-Ray MeSH
- Molecular Conformation MeSH
- Models, Molecular MeSH
- Drug Design * MeSH
- Boron Compounds chemical synthesis chemistry metabolism pharmacology MeSH
- Carbon chemistry MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- HIV Protease MeSH
- HIV Protease Inhibitors MeSH
- Cobalt MeSH
- Boron Compounds MeSH
- Carbon MeSH
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(2)N-(8-(C(2)H(4)O)(2)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))-3,3'-Co)(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.
References provided by Crossref.org
Cross-metathesis of allylcarboranes with O-allylcyclodextrins
PDB
3I8W
