Research Project
Grant-in-Aid for Challenging Exploratory Research
Using mass spectrometry and X-ray crystal structure analysis, we attempted toelucidate the dimerization dynamics of HIV -1 protease (PR). Our data showed that darunavir (DR V), anFDA-approved PR inhibitor, binds to both monomers and dimers of PR and blocks HIV -1 replication.We also showed that the introduction of DR V -resistance-associated amino acids into PR prevented DR Vfrom binding to PR monomers and decreased the amount of dimerized PR species. The data should be ofutility in not only examining the PR dimerization dynamics but also designing more potent PR inhibitorsthat hardly permit the emergence of DR V -resistant HIV -1 variants.
All 2013 2012
All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (7 results) Book (1 results)
Agents Chemother
Volume: 57 Issue: 5 Pages: 2036-2046
10.1128/aac.02189-12
Cell. Mol. Biol
Volume: 58 Pages: 187-195
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551986/
Journal of Virology
Volume: 86 Issue: 24 Pages: 13384-13396
10.1128/jvi.07234-11
AntimicrobAgents Chemother.
Volume: 56 Issue: 9 Pages: 4707-4712
10.1128/aac.00723-12
Expert Opin Emerging Drugs
Volume: 17 Issue: 2 Pages: 135-145
10.1517/14728214.2012.673584
Mol Pharmacol
Volume: 82 Issue: 1 Pages: 125-133
10.1124/mol.112.078758
Bioorganic &Medicinal Chemistry Letters
Volume: 22 Issue: 6 Pages: 2308-2311
10.1016/j.bmcl.2012.01.061
Angewandte Chemie International Edition in English
Volume: 51 Issue: 8 Pages: 1778-1802
10.1002/anie.201102762
Antimicrob Agents Chemother
Volume: 56 Issue: 3 Pages: 1630-1634
10.1128/aac.05729-11
Nucleic Acids Research
Volume: 40 Issue: 1 Pages: 345-359
10.1093/nar/gkr694