Synthesis and Biological-activity of the Mono-galactosyl-vespulakinin-1 and Di-galactosyl-vespulakinin-1 Analogs

Syntheses are described of some mono- and di-glycosylated analogues of vespulakinin 1. The solid phase procedure, based on the Fmoc chemistry, was used to prepare (Gal-alpha)Thr3-vespulakinin 1, (Gal-beta)Thr3-vespulakinin 1 and the di-glycosylated analogue ((Gal-alpha)Thr3, (Gal-alpha)Thr4-vespulakinin 1. The beta-glycosylated derivative was also prepared by the continuous flow variant of the Fmoc polyamide method. The synthesized glycopeptides were purified and characterized by amino acid analysis, optical rotation, analytical HPLC, H-1- and C-13-NMR and FAB-MS. Preliminary pharmacological experiments showed that the carbohydrate-free vespulakinin 1 is less active than bradykinin (about 0.3 times on a molar basis) when tested by guinea pig rectum contraction, and the two monoglycosylated analogues are equiactive (about 0.9 times the bradykinin activity). The most active derivative, the (Gal-alpha)Thr3, (Gal-alpha)Thr4-vespulakinin 1 analogue, was about 2.5 times as active as bradykinin.