[Show abstract][Hide abstract] ABSTRACT: The syntheses of two analogues related to the C-terminal nonapeptide amide sequence 25-33 of cholecystokinin-pankreozymin are described. Based on the primary structure of the CCK-PZ-active caerulein and the experiences gained from the methionine replacement with leucine or norleucine in human little gastrin I, the analogues were designed by substituting methionine 28 with threonine, and methionine 31 with leucine and norleucine, respectively. Using a new method for the synthesis of tyrosine-O-sulfate-containing peptides, developed in our laboratory, and applying acid-labile side-chain protection in combination with the benzyloxycarbonyl group, the fully protected nonapeptide amide derivatives Z-Arg(Z2)-Asp(OBut)-Tyr-(SO3Ba1/2)-Thr(But)-Gly-Trp-Leu-Asp(OBut)-Phe-NH2 and Z-Arg(Z2)-Asp(OBut)-Tyr(SO3-Ba1/2)-Thr(But)-Gly-Trp-Nle-Asp(OBut)-Phe-NH2, were obtained. Upon hydrogenolytic and subsequent acidolytic removal of the protecting groups, followed by purification via chromatographic procedures the nonapeptide amides were isolated in satisfactory yields at a high degree of purity. In vivo and in vitro assays showed that a substitution of methionine 31 by norleucine with concomitant replacement of methionine 28 by threonine produced a fully active analogue, whereas for the threonine 28, leucine 31 analogue the pankreozymin-activity was lowered by a factor 10.
No preview · Article · Aug 1981 · Hoppe-Seyler's Zeitschrift für physiologische Chemie
[Show abstract][Hide abstract] ABSTRACT: The synthesis is described of a suitably protected decapeptide derivative corresponding to the C-terminal tyrosin-O-sulfate-containing sequence 24--33 of cholecystokinin-pancreozymin as key fragment for the total synthesis of this gastrointestinal hormone or its 39-variant. This peptide derivative has been prepared according to our newly developed procedure based on the direct use of N-acyltyrosine-O-sulfate barium salt. Additionally, removal of the protecting groups followed by purification via chromatographic methods produced the decapeptide amide in good yields and with a high degree of purity as a fully active cholecystokinin-pancreozymin related peptide.
No preview · Article · Mar 1981 · Hoppe-Seyler's Zeitschrift für physiologische Chemie
[Show abstract][Hide abstract] ABSTRACT: The syntheses of the hexapeptide and octapeptide derivative corresponding to the sequences 9-14 and 1-8 of human-big-gastrin I, respectively, are described. The two fragments obtained predominantly by stepwise procedures, represent in the suitably protected form building blocks for the total syntheses of human-big-gastrin I and its 32-leucine-analogue.
No preview · Article · Nov 1979 · Monatshefte fuer Chemie/Chemical Monthly
[Show abstract][Hide abstract] ABSTRACT: A new synthetic route to tyrosine-O-sulfate-containing peptides based on the direct use of N alpha-acyltyrosine-O-sulfate is described and exemplified by the synthesis of the [Thr28,Leu31]cholecystokinin-pankreozymin-(25-33)-nonapeptide.
No preview · Article · Jul 1979 · Hoppe-Seyler's Zeitschrift für physiologische Chemie
[Show abstract][Hide abstract] ABSTRACT: Synthetic Peptide Hormones, Human Big Gastrin I. A new total synthesis of the tetratriacontapeptide amide corresponding to the proposed primary structure of human big gastrin I is described. The synthetic route was based on the preparation of six suitably protected fragments, related to sequence 28-34, 23-27, 21-22, 15-20, 9-14, and 1-8, to be used as building blocks for the total synthesis. The protecting groups were selected according to the Schwyzer-Wünsch strategy of maximum side chain protection based on tertiary alcohols, also for the imidazol function of histidine. Subsequent assembly of the six fragments by three different pathways using the highly efficient Wünsch-Weygand condensation procedure to ensure minimum racemization, followed by deprotection of the synthetic products via exposure to trifluoroacetic acid and final purification by ion-exchange chromatography on DEAE-Sephadex A-25 and partition chromatography on Sephadex G-25, led to human big gastrin I, homogeneous within the limits of the analytical methods used. The biological activity of the synthetic product proved to be 50 percent higher than that of human little gastrin I. The 32-leucine analogue of human big gastrin I was prepared in the same way.
No preview · Article · Jan 1977 · Zeitschrift fur Naturforschung. C, Journal of biosciences