牛乳κ-酪蛋白活性多肽及其改造肽的合成和生物活性

Synthesis and Bioactivity of Milk κ-Casein Active Peptides and Transformation Peptides

为获得抗凝血活性更强的多肽,对牛乳κ-酪蛋白(κ-CN)的十一肽(f106-116)进行设计合成并改造,采用Fmoc固相合成策略,以Wang树脂为载体,Fmoc保护氨基酸为原料,HOBT/DIC为缩合剂,TFA/苯甲硫醚/EDT/苯甲醚裂解体系脱除保护基,经RP-HPLC纯化后得到了纯度>95%的9种多肽,经ESI-MS确证其结构。将所有的合成肽进行凝血酶时间(TT)、活化部分凝血活酶时间(APTT)以及凝血酶原时间(PT)活性测定,结果表明,各改造肽抗凝活性皆低于十一肽,增强牛乳κ-CN的十一肽片段的疏水性,其TT活性增强。

In order to obtain peptides with higher anticoagulant activity, eleven peptide（f106-116） from milk k-ca-sein（k-CN） and its transformations were successfully synthesized according to its peptide sequence using Wangresin as a solid supporter with Fmoc-amino acids as raw materials and HOBT/DIC as condensing agent. Thepeptide was cleaved from the resin with the reagent of TFA/thioanisole/EDT/anisole. After purified by RP-HPLC,9 peptides with the purity above 95% were obtained and confirmed by an ESI-MS. The TT,APTT andPT activities of all synthetic peptides were measured. The anticoagulant activity of transformation peptide waslower than that of eleven peptide,whilst the activity of TT was enhanced with the increase of hydrophobicity ofeleven peptide from milk k-CN.