Paul Thamm

[Side-reactions in peptide synthesis, IV. Charactertzation of C- and C,N-teri-butylated tryptophan derivatives (author's transl)].

Besides Nin-tert-butylated tryptophan derivatives, other tert-butyl-tryptophan analoga are also found as a result of side-reactions accurring during the acidolytic cleavage of protecting groups being based on a tert-butyl moiety. C-mono-substitution could be detected as well as di- and tri-substitution. All these tert-butylated tryptophans could be isolated in a pure form from the tert-butylation mixture either free or as derivatives and could unequivocally be identified in particular by means of mass spectrometry and nuclear magnetic resonance spectroscopy.

Structure-function studies on gastrointestinal hormones: I. Synthesis of secretin analogs and their biological and immunological properties

Abstract Syntheses by conventional procedures of the three analogs corresponding to the porcine secretin sequence crossed at position 6 by the N-terminal hexapeptide sequences of VIP, GIP, and glucagon are described, viz., Ala 4 ,Val 5 -, Tyr 1 ,Ala 2 ,Glu 3 -, and Gln 3 -secretin (VIP-SN, GIP-SN, and GLU-SN). The analog Phe 1 ,Phe 2 ,Trp 3 ,Lys 4 -secretin (SOMA-SN), designed on the basis of the surprising homology of the sequence portions 10–13 of somatostatin and 5–8 of secretin, was also prepared. Finally, the synthesis of N α -3-(4-hydroxyphenyl)propionyl-β-alanyl-secretin (DATA-SN), a tracer suitable for secretin radioimmunoassay and as an N-terminus modified secretin analog, is reported. The analogs are compared, in terms of their biological and immunological properties in different assay systems, with pure synthetic secretin.

Total Synthesis of PHI

Abstract PHI has recently been isolated from porcine duodenum as a new peptide factor with VIP-like activities. Its primary structure corresponds to a linear heptacosapeptide amide characterized by a remarkable sequence homology to the other known members of the glucagon family. The synthesis of this hormone candidate has been performed applying the strategy of overall acid-labile side-chain protection and the fragment condensation procedure. Upon assembly of the fragments to the fully protected heptacosapeptide amide, acidolytic deprotection with trifluoroacetic acid followed by purification of the resulting crude product via ion exchange chromatography and partition chromatography yielded synthetic PHI at a high degree of purity as judged from different analytical tests. Comparative analyses of the synthetic and natural product by means of chromatographic and biological assays confirmed the identity of the two PHI preparations.

Zur Synthese von Human-Big-Gastrin I und seinem 32-Leucin-Analogon

The preparation of the pure tetratriacontapeptide amide <Glu-Leu-Gly-Pro-Gln-Gly-His-Pro-Ser-Leu-Val-Ala-Asp-Pro-Ser-Lys-Lys-Gln-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 (human big gastrin I) and the analogue Leu32-human big gastrin I from the crude synthetic materials obtained after deblocking of the overall protected tetratriacontapeptide amide derivatives by means of trifluoroacetic acid is described. The criteria for homogeneity obtained by chromatographic, electrophoretic, enzymatic and spectroscopic methods are reported.

Zur Synthese von Human-Big-Gastrin I und seinem 32-Leucin-Analogon 2. Mitteilung: Darstellung der Teilsequenzen 9–14 und 1–8

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.