Article ID Journal Published Year Pages File Type
1397513 European Journal of Medicinal Chemistry 2011 5 Pages PDF
Abstract

Through virtual screening of a rationally built database consisting of 40 peptides, we identified three short peptides. After testing these three synthetic peptides, we found that the peptide Trp-Gly-Pro (WGP) showed comparable inhibitory ability as positive control cyclosporine A (CsA) on CypA-mediated PPIase activity with IC50 values of 33.11 nM and 10.25 nM, respectively. The peptide WGP had same order of CypA-binding affinity as CsA with dissociation equilibrium constant KD of 3.41 × 10−6 and 6.42 × 10−6 M, respectively. This peptide could also inhibit HIV-1IIIB infection. This study provides a novel strategy for rational design and development of peptidic drugs.

Graphical abstractPeptidic inhibitor Trp-Gly-Pro binds to the active site of cyclophilin A by hydrophobic interactions and forming multiple hydrogen bonds.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Rationally design of a focused peptide library consisting of 40 peptides based on our previous findings. ► Three peptides were identified with the binding energy lower than the positive control CsA. ► WGP, one of the three selected peptides, showed comparable inhibitory ability as CsA on CypA-mediated PPIase activity. ► WGP had same order of CypA-binding affinity as CsA and could also inhibit HIV-1IIIB infection. ► A potent peptidic inhibitor WGP with low molecular size and low cytotoxicity was identified for CypA.

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