title: Blocking HIV-1 entry by a gp120 surface binding inhibitor.
abstract: We report the mode of action of a proteomimetic compound that binds to the exterior surface of gp120 and blocks HIV-1 entry into cells. Using a one cycle time-of-addition study and antibody competition binding studies, we have determined that the compound blocks HIV-1 entry through modulation of key protein-protein interactions mediated by gp120. The compound exhibits anti-HIV-1 replication activities against several pseudotype viruses derived from primary isolates and the resistant strains isolated from existing drug candidates with equal potency. Together, these data provide evidence that the proteomimetic compound represents a novel class of HIV-1 viral entry inhibitor that functions through protein surface recognition in analogy to an antibody.
authors.affiliation: Department of Chemistry, Yale University, New Haven, CT 06520, United States.
authors.forename: Lun K
authors.initials: LK
authors.lastname: Tsou
authors.forename: Chin-Ho
authors.initials: CH
authors.lastname: Chen
authors.forename: Ginger E
authors.initials: GE
authors.lastname: Dutschman
authors.forename: Yung-Chi
authors.initials: YC
authors.lastname: Cheng
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hamilton
mesh_terms: D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D011485:Protein Binding; D053586:Virus Internalization / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120