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. The amino-terminal octapeptide sequence of vespulakinin 1, Fmoc-Thr(tBu)-Ala-Thr(tBu)-Thr(tBu)-Arg(Pmc)-Arg(Pmc)-Arg(Pmc)-Gly-OH, and its N alpha-Boc-[(Gal beta)Thr3, (Gal beta)Thr4]-analogue, were used to prepare N alpha-(1-8 VSK 1)-cyclo-N epsilon-kallidin and N alpha-[(Gal beta)Thr3, (Gal beta)Thr4, 1-8 VSK 1]-cyclo-N epsilon-kallidin. Peptides and glycopeptides were characterized by amino-acid analysis, optical rotation, analytical HPLC and FAB-MS. Consistent with previous findings, preliminary pharmacological experiments on smooth muscle preparations showed that the cyclic, or partially cyclic, analogues were significatively less potent than the linear ones.
Gobbo
M
M
Biopolymer Research Centre, Department of Organic Chemistry, University of Padova, Italy.
Biondi
L
L
Filira
F
F
Piek
T
T
Rocchi
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry; D013329:Structure-Activity Relationship; D014862:Wasp Venoms / Q000138:chemical synthesis* / Q000494:pharmacology
D010456:Peptides, Cyclic; D014862:Wasp Venoms; C096176:bradykinin, cyclo-N(epsilon)-Lys-; C096177:vespulakinin 1, endo-Lys(8a)-; C054333:vespulakinin 1; C062689:bradykinin, Thr(6)-; D001120:Arginine; D001920:Bradykinin