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

采用新型合成策略合成大分子硫酸化肽激素

基本信息

批准号：
06672101
负责人：
KITAGAWA Kouki
金额：
$ 1.47万
依托单位：
Niigata College of Pharmacy
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

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.

1.在“日本的合成有机化学杂志”中开发和审查了一种有效采用安全切割型保护组的酪氨酸 - 含有肽的新方法。使用固体相碎片凝结方法合成弹药样抗菌肽。使用带有安全捕获型保护组的受保护片段。3。在固体辅助上使用片段凝聚方法，在固体辅助上，完全保护的肽与人类大胃蛋白（34氨基酸酸残基）相应的完全保护的肽是有效构建的。通过在TFA中用1M三甲基甲基甲硅烷 - 硫氨异异异异异异异异异异异异异异异异异异异异异异异异异，可在合理的纯度中获得。通过用TFA处理同一树脂，通过MSIB/MSZ保护组部分保护的肽，获得了硫化大胃蛋白的关键中间体。该受保护的肽转化为硫酸化肽（大胃蛋白II）。4。基于极酸的2-氯乙烯树脂，硫化肽，胃蛋白和胆囊蛋白相关的肽的关键脱落方法有效地制备了有效制备。该方法可以作为一种高效的固相合成方法来直接制备硫酸化肽。5。关于硫化肽质谱的一些有用信息是通过我们组制备的合成肽获得的。