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

1.开发了一种有效利用安全捕捉型保护基团合成含酪氨酸硫酸盐的多肽的新方法，并在《日本合成有机化学杂志》上进行了综述。2.建立了固相法制备安全捕捉型保护基多肽片段的方法。以含有安全捕捉型保护基团的保护片段为原料，采用固相片段缩合的方法合成Mainin样抗菌肽。3.利用固相载体上的片段缩合方法，有效地构建了与人大胃泌素(34个氨基酸残基)相对应的完全保护的多肽。该多肽树脂经1M三甲基溴化硅-硫代苯甲醚在TFA中处理后，得到纯度合理的人大胃泌素(非硫酸盐)。同样的树脂经TFA处理后，得到部分由MsiB/MSZ保护基团保护的多肽，MsiB/MSZ保护基团是合成大胃泌素的关键中间体。基于极不稳定的2-氯三丁基树脂和关键的去保护方法，高效地制备了胃泌素和缩胆囊素相关的多肽。该方法可以推广为一种高效的固相合成方法，用于直接制备硫酸化多肽。5.通过本课题组合成的多肽，获得了一些关于硫化多肽的有用信息。

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.