Synthesis, conformation and biological activity of linear and cyclic Thr6-bradykinin analogues containing N-benzylglycine in place of phenylalanine.

Three linear Thr6-bradykinin analogues in which either one or both the two phenylalanine residues in the peptide sequence have been substituted by N-benzylglycine (BzlGly) and their head-to-tail cyclic analogues were synthesized and tested on an isolated rat duodenum preparation. The linear (BzlGly5,Thr6-BK, BzlGly8,Thr6-BK and BzlGly(5,8),Thr6-BK) and the cyclic (cyclo BzlGly5,Thr6-BK, cyclo BzlGly8,Thr6-BK and cyclo BzlGly(5,8),Thr6-BK) peptoid-like analogues were characterized by amino acid analysis, optical rotation, analytical HPLC and MALDI-TOF mass spectroscopy. The conformational features of both the linear and cyclic derivatives were investigated by FT-IR and CD measurements.

Comparison of the immunogenicity of wasp venom peptides with or without carbohydrate moieties.

Three synthetic vespulakinin analogues either with or without carbohydrate moieties and mastoparan B isolated from Vespa basalis venom were investigated for their immunogenic activity and solution conformation. Mice immunized with these wasp venom peptides, with the exception of (Gal alpha)Thr3, (Gal alpha)Thr4-vespulakinin 1, showed positive antibody responses. However, the response elicited by mastoparan B was much higher than those induced by vespulakinin analogues.

Synthesis and biological activities of head-to-tail cyclic bradykinin analogues of varying ring size.

Syntheses of cyclic kinin analogues with different backbone atom numbers are described. Cyclization, by either the O-benzotriazolyl-N,N,N',N'-tetramethyluronium tetrafluoroborate/1-hydroxybenzotriazole/diisopropylethyl amine (TBTU-HOBt-DIPEA) or the diphenylphosphoryl azide (DPPA) procedure of linear peptides prepared by the solid-phase method based on the g-fluorenyl methyloxycarbonyl chemistry, was used for preparing cyclo-Gly-Ile-Ile-Gly-bradykinin, cyclo-Lys-kallidin (cyclo-Lys-Lys-bradykinin) and cyclo-des Arg-bradykinin. Peptides were characterized by amino acid analysis, optical rotation, analytical high-performance liquid chromatography and matrix-assisted laser desorption ionization-time flight mass spectrometry.

B2-kininergic action of linear and cyclic tryptophan6- and tyrosine6-kallidin.

This study was undertaken to determine the importance of the central aromatic moiety in the kallidin and cyclokallidin molecules, using the relaxation of the isolated duodenum of the rat. Replacement in kallidin of the central phenylalanine by tryptophan increased the potency from an EC50 of 3 x 10(-10)M to 2 x 10(-12)M. Replacement by tyrosine decreased the potency to an EC50 of 8 x 10(-8)M.

Cyclic analogues of Thr6-bradykinin, N epsilon-Lys-bradykinin and endo-Lys8a-vespulakinin 1.

Syntheses are described of the endo-Lys8a-vespulakinin 1 and of cyclo-Thr6- and cyclo-N epsilon-Lys-bradykinin. The linear peptides covering the entire sequences of endo-Lys8a-VSK-1 and Thr6-BK, and the decapeptide containing all residues constituting Lys-BK, with a Arg-Lys peptide bond involving the epsilon-amino function of lysine, were prepared by the solid-phase procedure based on Fmoc chemistry. Cyclization was carried out by the diphenylphosphorazide method.