Thioxo Analog Of Insect Kinin: Synthesis, Characterization, And Conformation-activity Correlation Study

The insect kinins share a highly conserved C-terminal pentapeptide sequence Phe-Xaa-Yaa-Trp-Gly-NH₂,where Xaa can be Tyr,His,Ser or Asn,and Yaa can be Ala but is generally Ser or Pro.They have been isolated from a number of insects, including species of Dictyoptera,Lepidoptera,and Orthoptera.Structurally,the insect kinins require an intact C-terminal pentapeptide sequence for full bioactivity, which was therefore designated as the active core sequence.Conformation studies indicated that there are two distinct conformation with aβ-turn over residue 1-4 and 2-5,respectively.In order to obtain a more direct evidence for the active one of these two distinct conformations,a kinin analog containing a thioxopeptide bondΨ[CS-N], a nearly isosteric modification of the native peptide bond,which can be used as a photoswitch,was synthesized.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(t_1/2=40 min) permitted us to determine the cockroach hindgut myotropic activity of the thioxopeptide in photostationary state.The results indicated that the activity increased significantly after UV irradiation and recovered to the ground level after thermal re-equilibration.In the present work,which utilizing the phototriggered isomerization in a specific position of peptide backbone,revealed that the cisΨ[CS-N]²-kinin conformer is the active conformation when interact with kinin receptor on cockroach hindgut.