Synthesis and biological activity of the mono- and di-galactosyl-vespulakinin 1 analogues

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 α)Thr³-vespulakinin 1, (Galβ)Thr³-vespulakinin 1 and the di-glycosylated analogue ((Gal α)Thr³. (Gal α)Thr⁴-vespulakinin 1. The β-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, ¹H-and ¹³C-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 α)Thr³, (Gal α)Thr⁴-vespulakinin 1 analogue, was about 2.5 times as active as bradykinin.