The Department of Polymer Science and Engineering and §The Department of Chemistry and Biochemistry, The University of Southern Mississippi , Hattiesburg, Mississippi 39406, United States.
Biomacromolecules. 2013 Oct 14;14(10):3793-9. doi: 10.1021/bm401205y. Epub 2013 Oct 2.
A facile synthetic pathway for preparing block copolymers with pH-responsive L-glutamic acid segments for membrane disruption is reported. Aqueous reversible addition-fragmentation chain transfer (aRAFT) polymerization was first used to prepare biocompatible, nonimmunogenic poly[N-(2-hydroxypropyl)methacrylamide]. This macro chain transfer agent (CTA) was then converted into a macroinitiator via simultaneous aminolysis and thiol-ene Michael addition using the primary amine substituted N-(3-aminopropyl)methacrylamide. This macroinitiator was subsequently utilized in the ring-opening polymerization of the N-carboxyanhydride monomer of γ-benzyl-L-glutamate. After deprotection, the pH-dependent coil-to-helix transformations of the resulting HPMA-b-(L-Glu) copolymers were monitored via circular dichroism spectroscopy. HPMA segments confer water solubility and biocompatibility while the L-glutamic acid repeats provide reversible coil-to-helix transitions at endosomal pH values (~5-6). The endolytic properties of these novel [HPMA-b-(L-Glu)] copolymers and their potential as modular components in drug carrier constructs was demonstrated utilizing red blood cell hemolysis and fluorescein release from POPC vesicles.
本文报道了一种用于制备具有 pH 响应 L-谷氨酸片段的嵌段共聚物的简便合成途径，用于膜破坏。首先使用水性可逆加成-断裂链转移（aRAFT）聚合制备生物相容、非免疫原性的聚[N-(2-羟丙基)甲基丙烯酰胺]。然后，通过使用取代的伯胺的 N-(3-氨丙基)甲基丙烯酰胺的同时氨解和硫醇-烯迈克尔加成将这种大分子链转移剂（CTA）转化为大分子引发剂。随后，在 N-羧基酸酐单体 γ-苄基-L-谷氨酸的开环聚合中使用该大分子引发剂。脱保护后，通过圆二色光谱监测所得 HPMA-b-(L-Glu)共聚物的 pH 依赖性构象从无规线团到螺旋的转变。HPMA 片段赋予水溶性和生物相容性，而 L-谷氨酸重复序列在内涵体 pH 值（约 5-6）下提供可逆的无规线团到螺旋的转变。利用红细胞溶血和 POPC 囊泡中荧光素的释放，证明了这些新型[HPMA-b-(L-Glu)]共聚物的内溶性质及其作为药物载体构建模块的潜在用途。
