Syntheses of Big-Molecular-Form Sulfated Peptide Hormones Using Novel Synthetic Strategy

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1.A novel approach for the synthesis of tyrosine-sulfate containing peptides, in which the safety-catch-type protecting groups were effectively employed, was developed and reviewed in the "Journal of Synthetic Organic Chemistry in Japan".2.A solid-phase method for the preparation of the peptide fragments protected with the safety-catch-type protecting groups was newly developed. Magainin-like antimicrobial peptide was synthesized by the solid-phase fragment condensation approach using the protected fragments bearing the safety-catch-type protecting groups.3.Using a fragment condensation approach on the solid-support, the fully protected peptide corresponding to human big gastrin (34 amino acid residue) was effectively constructed. By the treatment of this peptide resin with 1M trimethylsilylbromide-thioanisole in TFA,human big gastrin (non-sulfate) was obtained in a reasonable purity. While by the treatment of the same resin with TFA,the peptide partially protected with the Msib/Msz protecting groups, the key intermediate for the sulfated big gastrin, was obtained. Conversion of this protected peptide to the sulfated peptide (big gastrin-II) is in progress.4.Based on an extremely acid-labile 2-chlorotrityl resin and the critical deprotection method for the sulfated peptides, gastrin and cholecystokinin-related peptides were efficiently prepared. This approach can be extended as a highly efficient solid-phase synthetic approach for the direct preparation of the sulfated peptides.5.Some useful information concerning the mass spectrum of the sulfated peptides were obtained through synthetic peptides prepared by our group.