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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.

SUBMITTER: Muppidi A

PROVIDER: S-EPMC4005879 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Design of antiviral stapled peptides containing a biphenyl cross-linker.

Muppidi Avinash A Zhang Hongtao H Curreli Francesca F Li Nan N Debnath Asim K AK Lin Qing Q

Bioorganic & medicinal chemistry letters 20140222 7

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 bin ...[more]

PMID: 24613163

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