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.
Gobbo
M
M
Department of Organic Chemistry, University of Padova, Italy.
Biondi
L
L
Filira
F
F
Rocchi
R
R
Piek
T
T
D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D006168:Guinea Pigs; D007705:Kinins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009904:Optical Rotation; D010456:Peptides, Cyclic / Q000737:chemistry; D014862:Wasp Venoms / Q000737:chemistry* / Q000302:isolation & purification
D007705:Kinins; D010456:Peptides, Cyclic; D014862:Wasp Venoms