比伐卢定的聚乙二醇化修饰

摘要

将比伐卢定(BVLD)多肽链7-甘氨酸(Gly)用半胱氨酸(Cys)取代,以聚乙二醇(PEG)定点修饰巯基,采用多肽固相会成法制得[Cys]7-BVLD(2)；2与mPEG-MAL(3a～3c)偶联合成了三个聚乙二醇化修饰的比伐卢定衍生物—[Cys (mPEG2000-MAL)]7-BVLD (1a),[Cys(mPEG5000-MAL)]7-BVLD( 1b)和[Cys(mPEG10000-MAL)]7-BVLD(1c),其结构经MS确证.PT和TT评价结果表明,1a～1c均表现出良好的抗凝活性,尤其是1b的抗凝活性优于比伐卢定.%Three PEGylation bivalirudin ( BVLD) derivatives, [ Cys (mPEG2000-MAL) ]7-BVLD (la), [Cys(mPEG5000-MAL)]7-BVLD(lb) and [Cys(mPEGlOOOO-MAL) ]7-BVLD(lc) , were synthesized by addition reaction of mPEG-MAL(3a ~3c) and [Cys]7-BVLD(2) which was prepared by replacing the 7-glycine(Gly) of BVLD by cysteine(Cys) with the solid phase peptide synthesis. The structures were confirmed by MS. The results of PT and TT evaluation showed that la ~ lc exhibited good anticoagulation activities, especially lb was better than bivalirudin.