Identification of a beta3-peptide HIV fusion inhibitor with improved potency in live cells.
We recently reported a beta(3)-decapeptide, betaWWI-1, that binds a validated gp41 model in vitro and inhibits gp41-mediated fusion in cell culture. Here we report six analogs of betaWWI-1 containing a variety of non-natural side chains in place of the central tryptophan of the WWI-epitope. These analogs were compared on the basis of both gp41 affinity in vitro and fusion inibition in live, HIV-infected cells. One new beta(3)-peptide, betaWXI-a, offers a significantly improved CC(50)/EC(50) ratio in the live cell assay.
Bautista
Arjel D
AD
Department of Chemistry, Yale University, New Haven, CT 06520, USA.
Stephens
Olen M
OM
Wang
Ligong
L
Domaoal
Robert A
RA
Anderson
Karen S
KS
Schepartz
Alanna
A
D002460:Cell Line; D015700:HIV Envelope Protein gp41 / Q000378:metabolism; D023581:HIV Fusion Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010455:Peptides; C514787:gp41 protein, Human immunodeficiency virus 1