A photoswitchable thioxopeptide bond facilitates the conformation-activity correlation study of insect kinin

Abstract

Thioxopeptide bond Ψ[CS-N], a nearly isosteric modification of the native peptide bond, was introduced into insect kinin active core pentapeptide to evaluate the impact of backbone cis/trans photoswitching on bioactivity. The thioxo analog Phe1-Tyr2-Ψ[CS-N]-Pro3- Trp4-Gly5-NH2 (Ψ[CS-N]2-kinin), was synthesized by Fmoc solid-phase peptide strategy. The reversible photoswitching property was characterized via spectroscopic methods and HPLC, which showed that the cis conformer increased from 15.7 to 47.7% after 254 nm UV irradiation. A slow thermal reisomerization (t1/2 = 40 min) permitted us to determine the cockroach hindgut myotropic activity of the thioxopeptide in the photostationary state. The results indicated that the activity increased signicantly after UV irradiation and recovered to the ground level after thermal re-equilibration. In the present study, by utilizing the phototriggered isomerization in a specific position of peptide backbone, we revealed that the cis Ψ[CS-N]2-kinin conformer is the active conformation when interacting with kinin receptor on cockroach hindgut. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.