Cyclic analogues of wasp kinins from Vespa analis and Vespa tropica.

Syntheses are described of two bradykinin-like kinins isolated from Vespa analis (G-R-P-P-G-F-S-P-F-R-V-I, VSK-A) and Vespa tropica (G-R-P-Hyp-G-F-S-P-F-R-V-V, VSK-T) and of their cyclic analogues. Linear dodecapeptides were prepared by the solid-phase procedure based on Fmoc-chemistry, and cyclization was carried out by the diphenyl-phosphorylazide method. Peptide were characterized by amino acid analysis, optical rotation, analytical HPLC and FAB-MS. The conformational features of the cyclic and linear kinins were determined by circular dichroism measurements in water, 95% trifluoroethanol and 8 M guanidinium chloride. Consistent with previous findings, preliminary pharmacological experiments on smooth muscle preparations showed that cyclic wasp kinins were 50-100 times less potent than their linear analogues. Moreover, cyclo-VSK-A and cyclo-VSK-T behave like kininase inhibitors by preventing the degradation of straight kinins.