含 RGD 四肽的合成与功能

STUDIES ON THE SYNTHESIS AND ACTIVITIES OF RGD RELATED PEPTIDES

摘要: 在血小板依赖的血栓形成中,纤维蛋白与血小板表面GP II_b/III_a受体结合是重要步骤。在受体识别中,RGD(Arg-Gly-Asp,精·甘·天冬)是关键序列。含RGD多肽的竞争抑制作用,表现为抗血栓作用。本文合成了RGDS,RGDV和RGDF3种四肽;测定了它们的舒血管活性和抗血栓活性;讨论了溶液中的构象对生物活性的影响。在大鼠血栓模型上,用5.0μmol·kg^-1剂量,RGDS和RGDV无明显的抗血栓作用。用25μmol·kg^-1剂量,RGDF的抗血栓作用有明显的统计意义。该结果与它们在溶液中的构象相关。3种四肽对主动脉条的舒血管作用体现另一种趋势,RGDS和RGDV显示明确的舒血管活性。小剂量时RGDF的舒血管作用与对照组相比,无统计学意义。

Abstract: In the binding of Fgn to GP IIb/IIIa, RGD is the key sequence. In the present paper, RGDS, RGDV and RGDF were synthesized by use of solution method. Bioassay indicated that the C-terminal amino acid residues were very important for their antithrombosis effects. Conformational studies showed that their antithrombosis potency may depend on their total energies.The observation of their vasodilation effects suggests that this kind of function is worthy to be further studied.