Antithrombogenic properties of bioconjugate streptokinase-polyglycerol dendrimers
Antithrombogenic properties of bioconjugate streptokinase-polyglycerol dendrimers
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DOI：
10.1007/s10856-006-6813-5
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发表时间：
2006-02-01
影响因子：
3.7
通讯作者：
San Román, J
中科院分区：
文献类型：
--
作者：
Fernandes, EGR;De Queiroz, AAA;San Román, J
树枝状大分子是一种单分散、球形、超支化的合成大分子，具有大量的表面基团，可以通过共价键合或电荷转移络合作用作为药物固定化的载体。在这项工作中，链激酶和聚甘油树枝状聚合物（PGLD）第5代的生物缀合物用于获得纤维蛋白溶解表面。PGLD树枝状大分子是通过使用聚甘油作为核心官能团的去质子化缩水甘油的开环聚合在称为发散合成的逐步生长过程中合成的。通过凝胶渗透色谱（GPC）、核磁共振（H-1-NMR、C-13-NMR）和基质辅助激光解吸电离（MALDI-TOF）技术证实了PGLD的树枝状结构。所合成的树枝状大分子呈现出低分散的分子量（Mw/Mn = 1.05）和0.82的支化度，表征了聚合物树枝状结构。通过体外试验（如血小板粘附和血栓形成）评价生物缀合物PGLD-Sk的血液相容性。使用未包被的聚苯乙烯-微量滴定板（ELISA）作为参考。落射荧光显微镜结果表明，PGLD-Sk涂层相对于未涂覆的ELISA板显示出改善的抗血栓形成特性。(c)2006 Springer Science + Business Media，Inc.
Dendrimers are monodisperse, spherical and hyperbranched synthetic macromolecules with a large number of surface groups that have the potential to act as carriers for drug immobilization by covalent binding or charge transfer complexation. In this work, a bioconjugate of streptokinase and a polyglycerol dendrimer (PGLD) generation 5 was used to obtain fibrinolytic surfaces. The PGLD dendrimer was synthesized by the ring opening polymerization of deprotonated glycidol using polyglycerol as core functionality in a step-growth processes denominated divergent synthesis. The PGLD dendritic structure was confirmed by gel permeation chromatography (GPC), nuclear magnetic resonance (H-1-NMR, C-13-NMR) and matrix assisted laser desorption/ionization (MALDI-TOF) techniques. The synthesized dendrimer presented low dispersion in molecular weights (M-w/M-n = 1.05) and a degree of branching of 0.82 which characterize the polymer dendritic structure. The blood compatibility of the bioconjugate PGLD-Sk was evaluated by in vitro assays such as platelet adhesion and thrombus formation. Uncoated polystyrene -microtitre plates (ELISA) was used as reference. The epifluorescence microscopy results indicate that PGLD-Sk coating showed an improved antithrombogenic character relative to the uncoated ELISA plates. (c) 2006 Springer Science + Business Media, Inc.