Synthesis of C-terminal fragments of bombesin and their analogues

With the aim of structural-functional studies in the bombesin series, a number of bombesin fragments and analogues have been synthesized. The synthesis was performed by the carbodiimide method and by the activated-ester method. Fragments with the sequences 7–14, 8–14, and 9–14 were obtained by 4+4, 3+4, and 2+4 schemes and a pentapeptide with the sequence 9–13 by a 3 + 2 scheme. Acetylation of the octapeptide BN(7–14) was carried out by the action of acetic anhydride in pyridine. Analogues of the C-terminal nonapeptide of bombesin [DPhe⁷]BN(6–14) and [Pro⁶, Gly⁷, DAla¹¹]BN(6–14) were synthesized by fragment condensation using the 5 + 4 scheme. The individuality of the compounds obtained was confirmed by their chromatographic behavior on plates coated with silica gel, and by the results of amino acid analysis, high-voltage electrophoresis, and high-performance liquid chromatography, and their structures were confirmed by the results of high-resolution¹H NMR spectroscopy (360 MHz). In experiments on rabbits, in a dose of 1 µg with central administration the full hypothermic effect of bombesin was shown by the preparation [AcGln⁷]BN(7–14), while the preparation [DPhe⁷]BN(6–14) and [Pro⁶,Gly⁷,DAla¹¹]BN(6–14) possessed only a slight effect (1% of the activity of bombesin).Leningrad State University. Institute of Organic Synthesis, Latvian SSR Academy of Sciences, Riga. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 554–564, July–August, 1989.