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6611784 
Journal Article 
TOTAL SOLID-PHASE SYNTHESIS OF PORCINE GUT GASTRIN RELEASING PEPTIDE (GRP), A MAMMALIAN BOMBESIN 
Marki, W; Spiess, J; Tache, Y; Brown, M; Rivier, JE; , 
1981 
Yes 
Journal of the American Chemical Society
ISSN: 0002-7863
EISSN: 1520-5126 
AMER CHEMICAL SOC 
WASHINGTON 
103 
11 
3178-3185 
English 
WOS:A1981LS85100040 
Recently, gastrin releasing peptide (GRP), Ala-Pro-Val-Ser-Val-Gly-Gly-Gly-Thr-Val-Leu-Ala-Lys-Met-Tyr-Pro-Arg-Gly-Asn-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2, a mammalian bombesin, was isolated from porcine gastric mucosa and sequenced by McDonald et al.9 This polypeptide was manually synthesized by solid-phase methodology, using a benzhydrylamine- styrene-1 % divinylbenzene copolymer. Deprotection and cleavage from the resin were accomplished by HF. The crude peptide was purified by gel filtration and reverse-phase, high-performance liquid chromatography (RP-HPLC). Homogeneity of the synthetic peptide was demonstrated by RP-HPLC, sequence analysis, peptide mapping, and amino acid analysis. The peptide was further characterized by thin-layer chromatography, paper electrophoresis, optical rotation, ultraviolet spectroscopy, and 300-MHz Fourier transform proton nuclear magnetic resonance spectroscopy. The circular dichroism spectra of GRP indicated that the polypeptide chain was largely random with no evidence for -helical structure. The primary structure was confirmed by amino acid analysis of the tryptic peptide fragments, sequence analysis of GRP and its Met(O) derivative using a modified 890 C spinning-cup sequencer, and C-terminal end group determination. GRP released gastrin when administered systemically and decreased gastric acid secretion when given intracisternally in rats. GRP also mimicked CNS-mediated actions of bombesin to influence thermoregulation or glucoregulation, most likely because of the common C-terminal homology of these peptides. This assumption was supported by the observation that the synthetic acetylated octapeptide [Ac-His20]-GRP (20-27) showed pharmacological effects similar to those exhibited by GRP and amphibian bombesin. © 1981, American Chemical Society. All rights reserved.