Switching between allosteric and dimerization inhibition of HIV-1 protease.
Refining the functional groups on a phenethylamine moiety within an inhibitor of HIV-1 protease led to a switch in the mechanism of inhibition from competitive and allosteric to dimerization inhibition. Phenylether extensions to the phenethylamine group led to agents that target the dimerization interface of HIV-1 protease with high potency.
Bowman
Michael J
MJ
Department of Chemistry, Purdue University, West Lafayett, Indiana 47907, USA.
Byrne
Simon
S
Chmielewski
Jean
J
D000577:Amides / Q000737:chemistry; D001667:Binding, Competitive / Q000187:drug effects; D016333:HIV Protease / Q000737:chemistry*; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D008958:Models, Molecular; D010627:Phenethylamines / Q000737:chemistry; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000577:Amides; D017320:HIV Protease Inhibitors; D010627:Phenethylamines; D016333:HIV Protease