Discovery of a potent peptidic cyclophilin A inhibitor Trp-Gly-Pro

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 IC 50 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 K D of 3.41 × 10 −6 and 6.42 × 10 −6  M, respectively. This peptide could also inhibit HIV-1 IIIB infection. This study provides a novel strategy for rational design and development of peptidic drugs.