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.开发了一种新的合成含有酪氨酸硫酸盐的肽的方法，该方法有效地利用了安全捕获型保护基团，并在“Journal of Synthetic Organic Chemistry in Japan”上进行了综述。2.一种固体-新开发了用于制备受安全捕获型保护基团保护的肽片段的相法。利用带有安全锁式保护基的受保护片段，通过固相片段缩合法合成了类Magainin抗菌肽。 3.采用固相载体上的片段缩合法，合成了与人类大分子相对应的全保护肽。胃泌素（34个氨基酸残基）被有效构建。通过在TFA中用1M三甲基溴硅烷-茴香硫醚处理该肽树脂，获得了纯度合理的人大胃泌素（非硫酸盐）。而通过用TFA处理相同的树脂，得到了被Msib/Msz保护基部分保护的肽，这是硫酸化大胃泌素的关键中间体。这种受保护的肽向硫酸化肽（大胃泌素-II）的转化正在进行中。4.基于酸极不稳定的2-氯三苯甲基树脂和硫酸化肽的关键脱保护方法，胃泌素和胆囊收缩素相关肽被有效地准备好了。该方法可推广为直接制备硫酸化肽的高效固相合成方法。5.通过本课题组制备的合成肽，获得了有关硫酸化肽质谱的一些有用信息。