张麟, 孙娜
AuthorsHTML:张麟, 孙娜
AuthorsListE:Zhang Lin, Sun Na
AuthorsHTMLE:Zhang Lin, Sun Na
Unit:天津大学化工学院，天津 300072
Unit_EngLish:School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
Abstract_Chinese:抗血栓药物种类繁多, 但主要以血液中血小板和凝血因子为靶点, 因而可能破坏正常凝血系统平衡而导致出血风险．针对该问题, 前期以胶原蛋白为靶点, 通过仿生设计已获得七肽LWWNSYY, 经实验验证该七肽能够抑制血小板表面整联蛋白α₂ β₁与胶原蛋白的结合, 从而抑制血小板的黏附及后续血栓形成．但是, LWWNSYY的疏水性较高导致其生物利用度较低．因此, 利用两亲性的单甲氧基聚乙二醇-丁醛(m_5k-BAD)修饰LWWNSYY, 构建血栓纳米抑制剂m_5k-BAD-L, 并考察其与胶原蛋白的结合特性以及抑制血小板黏附的实际效果．结果表明, m_5k-BAD-L能有效改善LWWNSYY的生物利用度, 且有效结合胶原蛋白, K_d为(0.60±0.28) μmol/L, 因而有效抑制血小板黏附．研究结果有助于推动新型血栓纳米抑制剂的开发和利用．
Abstract_English:Many antithrombotic agents have been developed，usually targeted at the important factors in blood such as platelets and coagulation factors. However，these agents usually disturb the blood coagulation system，thus incurring the risk of bleeding. In our previous work，a heptapeptide LWWNSYY targeted at exposed collagen on diseased blood vessel was obtained by biomimetic design. It was proven capable of blocking the binding of integrin α₂ β₁ on collagen，thus inhibiting platelet adhesion and subsequent thrombus formation. However，its bioavailability was limited due to its high hydrophobicity. Therefore，LWWNSYY was conjugated with amphiphilic methoxy polyethylene glycol-butyl aldehyde(m_5k-BAD)to prepare antithrombotic nanoconjugate(m_5k-BAD-L). Interactions between m_5k-BAD-L and collagen was then examined，as well as the efficiency of inhibiting platelet adhesion. It is shown that m_5k-BAD-L can effectively improve the bioavailability of LWWNSYY and binding capacity on collagen，with a K_d of (0.60±0.28) μmol/L，thus efficiently inhibiting the platelet adhesion. These results would be helpful for the development of nanomedicine for thrombus formation.
Keyword_Chinese:血栓抑制剂; 胶原蛋白; 血小板黏附; 溶解性; mPEG修饰
Keywords_English:thrombotic inhibitor; collagen; platelet adhesion; solubility; mPEG modification

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