[Syntheses of human little gastrin-I and its leucine-15, norleucine-15 and methoxinine-15 analogs].

Human little gastrin-I is known to exhibit a high tendency to air-oxidation of its methionine-15 residue to the corresponding S-oxide derivative, with concomitant loss of biological activity. Since its leucine-15 analog, even if fully biologically active, differs significantly from the parent hormone in the immunological properties, the norleucine-15 and methoxinine-15 analogues were synthetized. For the required comparative analyses new syntheses of human little gastrin-I and of its leucine-15 analog were additionally elaborated.

[Total synthesis of human big gastrin I. Revised primary structure (author's transl)].

The synthesis of the tetratriacontapeptide amide corresponding to the revised structure of human big gastrin I is described. The fully protected peptide derivative was obtained by assembly in sequence order of the suitably protected fragments [1--9], [10--14] and [15--34] via the dicyclohexylcarbodiimide/N-hydroxysuccinimide and azide method, respectively. Upon removal of the protecting groups by exposure to trifluoroacetic acid and purification of the resulting crude product by chromatographic methods, human big gastrin I was obtained in satisfactory yields and at a high degree of purity.

[Total synthesis of human big gastrin I and the 32-leucine analogue (author's transl)].

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 synthesis of motilin, II: Preparation of the complete sequences of [13-norleucine] motilin and [13-leucine] motilin (author's transl)].

Syntheses of two analogs of the intestinal hormone motilin containing in position 13 norleucine and leucine, respectively, are described. For this purpose a suitably protected octapeptide-derivative, corresponding to the sequence 1-8, was prepared and condensed with the tetradecapeptides 9-22 of [13-norleucine]-motilin and [13-leucine] motilin (described in the preceding paper) to give to overall protectdd docosapeptides Boc-Phe-Val-Pro-IIe-Phe-Thr-(But)-Tyr(But)-Gly-Glu(OBut)-Leu-Gln-Arg-(HBr)-Nle-Glu(OBut)-Glu(OBut)-Lys(Boc)-Glu-(OBut)-Arg(HBr)-Asn-Lys(Boc)-Gly-Gln-OBut and its 13-leucine analog.

[The synthesis of motilin, I: Preparation of the sequence fragments 9 - 22 of [13-norleucine]motilin and [13-leucine]motilin (author's transl)].

The syntheses of two suitably protected tetradecapeptides corresponding to the sequences 9 - 22 of [13-norlecucine] motilin [H-Glu(OBut)-Leu-Gln-Arg(HBr)-Nle-Glu(OBut)-Glu(OBut)-Lys(Boc)-Glu(OBut)-Arg(HBr-Asn-Lys(Boc)-Gly-Gln-OBu] and [13-leucine] motilin, respectively, are described. The two building blocks for the total syntheses of the motilin analogs were obtained by fragment-condensation of smaller units, prepared by stepwise procedure and corresponding to the sequences 18 - 22, 14 - 17, 12 - 13 (norleucine- and leucine-derivatives) and 9 - 11.