TOTAL SOLID-PHASE SYNTHESIS OF PORCINE GUT GASTRIN RELEASING PEPTIDE (GRP), A MAMMALIAN BOMBESIN
Marki, W; Spiess, J; Tache, Y; Brown, M; Rivier, JE; ,
| HERO ID | 6611784 |
|---|---|
| In Press | No |
| Year | 1981 |
| Title | TOTAL SOLID-PHASE SYNTHESIS OF PORCINE GUT GASTRIN RELEASING PEPTIDE (GRP), A MAMMALIAN BOMBESIN |
| Authors | Marki, W; Spiess, J; Tache, Y; Brown, M; Rivier, JE; , |
| Journal | Journal of the American Chemical Society |
| Volume | 103 |
| Issue | 11 |
| Page Numbers | 3178-3185 |
| Abstract | 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. |
| Doi | 10.1021/ja00401a040 |
| Wosid | WOS:A1981LS85100040 |
| Url | https://www.scopus.com/inward/record.uri?eid=2-s2.0-0019506636&doi=10.1021%2fja00401a040&partnerID=40&md5=068f3d7d63ad963ec5ea6feeeccc5324 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |