title: Design of antiviral stapled peptides containing a biphenyl cross-linker.
abstract: Here we report the design and synthesis of a panel of stapled peptides containing a distance-matching biphenyl cross-linker based upon a peptide capsid assembly inhibitor reported previously. Compared with the linear peptide, the biphenyl-stapled peptides exhibited significantly enhanced cell penetration and potent antiviral activity in the cell-based infection assays. Isothermal titration calorimetry and surface plasmon resonance experiments revealed that the most active stapled CAI peptide binds to the C-terminal domain of HIV capsid protein as well as envelop glycoprotein gp120 with low micromolar binding affinities, and as a result, inhibits both the HIV-1 virus entry and the virus assembly.
authors.affiliation: Department of Chemistry, State University of New York at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Avinash
authors.initials: A
authors.lastname: Muppidi
authors.affiliation: Laboratory of Molecular Modeling and Drug Design, Lindsley F. Kimball Research Institute of the New York Blood Center, 310 E 67th Street, New York, NY 10065, USA.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Modeling and Drug Design, Lindsley F. Kimball Research Institute of the New York Blood Center, 310 E 67th Street, New York, NY 10065, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Curreli
authors.affiliation: Department of Chemistry, State University of New York at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Modeling and Drug Design, Lindsley F. Kimball Research Institute of the New York Blood Center, 310 E 67th Street, New York, NY 10065, USA. Electronic address: adebnath@nybloodcenter.org.
authors.forename: Asim K
authors.initials: AK
authors.lastname: Debnath
authors.affiliation: Department of Chemistry, State University of New York at Buffalo, Buffalo, NY 14260, USA. Electronic address: qinglin@buffalo.edu.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000737:chemistry*; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D001713:Biphenyl Compounds; D003432:Cross-Linking Reagents; D010455:Peptides; C010574:biphenyl
keywords: HIV capsid; Peptides; Protein–protein interaction; Virus assembly; Virus entry