2. Academic Validation
  3. Design of antiviral stapled peptides containing a biphenyl cross-linker

Design of antiviral stapled peptides containing a biphenyl cross-linker

  • Bioorg Med Chem Lett. 2014 Apr 1;24(7):1748-51. doi: 10.1016/j.bmcl.2014.02.038.
Avinash Muppidi 1,  Hongtao Zhang 2,  Francesca Curreli 2,  Nan Li 1,  Asim K Debnath 3,  Qing Lin 4
Affiliations

Affiliations

  • 1 Department of Chemistry, State University of New York at Buffalo, Buffalo, NY 14260, USA.
  • 2 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.
  • 3 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: [email protected].
  • 4 Department of Chemistry, State University of New York at Buffalo, Buffalo, NY 14260, USA. Electronic address: [email protected].
PMID: 24613163 DOI: 10.1016/j.bmcl.2014.02.038
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.

Keywords

HIV capsid; Peptides; Protein–protein interaction; Virus assembly; Virus entry.

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