title: Discovery of HIV fusion inhibitors targeting gp41 using a comprehensive α-helix mimetic library.
abstract: The evaluation of a comprehensive α-helix mimetic library for binding the gp41 NHR hydrophobic pocket recognizing an intramolecular CHR α-helix provided a detailed depiction of structural features required for binding and led to the discovery of small molecule inhibitors (K(i) 0.6-1.3 μM) that not only match or exceed the potency of those disclosed over the past decade, but that also exhibit effective activity in a cell-cell fusion assay (IC(50) 5-8 μM).
authors.affiliation: Department of Chemistry, Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, United States.
authors.forename: Landon R
authors.initials: LR
authors.lastname: Whitby
authors.forename: Kristopher E
authors.initials: KE
authors.lastname: Boyle
authors.forename: Lifeng
authors.initials: L
authors.lastname: Cai
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Yu
authors.forename: Miriam
authors.initials: M
authors.lastname: Gochin
authors.forename: Dale L
authors.initials: DL
authors.lastname: Boger
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry*; D055808:Drug Discovery; D015700:HIV Envelope Protein gp41 / Q000378:metabolism*; D023581:HIV Fusion Inhibitors / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D018716:Molecular Mimicry; D015394:Molecular Structure; D017433:Protein Structure, Secondary; D054852:Small Molecule Libraries / Q000737:chemistry*
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D054852:Small Molecule Libraries