Synthesis of C-terminal fragments of bombesin and their analogues
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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).
KeywordsDipeptide Bombesin Preparative HPLC Vasoactive Peptide Main Spot
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- 2.R. Castiglione, F. Angelucci, V. Erspamer, G. F. Erspamer, and L. Negri, in: Peptides 1972 (eds. H. Hanson and H.-D. Jakubke), North-Holland, Amsterdam (1973), p. 463.Google Scholar
- 4.I. L. Kuranova, S. I. Churkina, N. G. Kovaleva, V. L. Lyudmirova, E. B. Filonova, A. T. Mar'yanovich, and V. F. Martynov, in: Abstracts of Lectures at the VIth All-Union Symposium on the Chemistry of Proteins and Peptides [in Russian], Zinatne, Riga (1983), p. 347.Google Scholar
- 8.M. Bodanszki, Synthesis, 333 (1981).Google Scholar
- 10.G. A. Fletcher and G. A. Jones, Int. J. Peptide Prot. Res.,4, No. 3, 347 (1972).Google Scholar
- 11.G. A. Fletcher and G. A. Jones, Int. J. Peptide Prot. Res.,7, No. 2, 91 (1975).Google Scholar
- 12.L. Bernardi, G. Bosisio, R. Castiglione, O. Goffredo, and F. Chillemi, Gazz. Chim. Ital.94, 853 (1964).Google Scholar