Catalytic generation of nitric oxide from S-nitrosothiols using immobilized organoselenium species
Catalytic generation of nitric oxide from S-nitrosothiols using immobilized organoselenium species
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DOI：
10.1016/j.biomaterials.2006.08.019
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发表时间：
2007-01-01
期刊：
影响因子：
14
通讯作者：
Meyerhoff, Mark E.
中科院分区：
文献类型：
--
作者：
Cha, Wansik;Meyerhoff, Mark E.
描述了具有固定化有机硒物种的产生一氧化氮(NO)的新型聚合物材料。这些材料模拟了有机硒小分子以及已知的含硒酶谷胱甘肽过氧化物酶(GPx)的能力，通过催化将S-亚硝硫醇(RSNO)分解为NO和相应的游离硫醇。模型聚合物材料，例如纤维素滤纸和聚乙烯亚胺，用适当的共价连接到聚合物结构的二硒化物物种进行修饰。这种有机硒(RSe)衍生聚合物被证明在适当的硫醇还原剂(例如谷胱甘肽)存在的情况下从RSNO物种产生NO。在使用非固定化形式的小有机二硒化合物的单独均相液相实验中推断，固定化的硒/硒和二硒化物物种可能通过催化途径参与了NO的产生。新RSE聚合物的初步实验清楚地证明了这种材料即使在与新鲜动物血浆接触后也能从RSNO物种中产生NO。由于NO具有抑制血小板黏附和活化的能力，预计血液中内源性S-亚硝硫醇产生的这种NO可以使含RSe的聚合物材料在与流动的血液接触时更具抗血栓能力。(C)2006爱思唯尔有限公司。保留所有权利。
Novel nitric oxide (NO) generating polymeric materials possessing immobilized organoselenium species are described. These materials mimic the capability of small organoselenium molecules as well as a known selenium-containing enzyme, glutathione peroxidase (GPx), by catalytically decomposing S-nitrosothiols (RSNO) into NO and the corresponding free thiol. Model polymeric materials, e.g., cellulose filter paper and polyethylenimine, are modified with an appropriate diselenide species covalently linked to the polymeric structures. Such organoselenium (RSe)-derivatized polymers are shown to generate NO from RSNO species in the presence of an appropriate thiol reducing agent (e.g., glutathione). The likely involvement of both immobilized selenol/selenolate and diselenide species for NO production is suggested via a catalytic pathway, as deduced in separate homogeneous solution phase experiments using nonimmobilized forms of small organodiselenide species. Preliminary experiments with the new RSe-polymers clearly demonstrate the ability of such materials to generate NO from RSNO species even after the contact with fresh animal plasma. It is anticipated that such NO generation from endogenous S-nitrosothiols in blood could render RSe-containing polymeric materials more thromboresistant when in contact with flowing blood, owing to NO's ability to inhibit platelet adhesion and activation. (c) 2006 Elsevier Ltd. All rights reserved.