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具有模拟SOD功能的大分子
SOD Mimics Based on Macromolecules
生命活动中用于维持生物体内超氧阴离子自由基动态平衡的超氧化物歧化酶(superoxide dismutase, SOD)是一类金属酶,属于典型的生物大分子金属络合物,因其在生命活动中所起的重要作用而备受关注。目前,有关SOD的模拟已从小分子化合物的模拟,走向大分子环境与活性中心相结合的系统模拟。本文从高分子化合物角度对模拟SOD的研究进展作一综述,以期为设计并开发具有生物相容且高活性的新型高分子抗氧化剂提供新思路。天然大分子有蛋白质与多肽、多糖、分子聚集体,目前所采用的蛋白质(多肽)是性能稳定的天然蛋白质或通过基因重组技术生物合成的蛋白质或多肽,所采用的多糖类物质主要有右旋糖酐、羧甲基纤维素、壳聚糖等。小分子活性化合物(如金属卟啉、新型肟类为配体的同核与异核复合物、salen型金属配合物等)通过与这些天然大分子结合,在提高活性的同时也改善了其稳定性。将活性小分子物质与分子聚集体(如胶束、脂质体)结合制得的SOD模拟物可以模拟天然SOD在体内的环境,提高抗氧化活性和体内循环时间。合成高分子模拟SOD的工作主要集中于高分子接枝金属配合物的研究,其中典型的合成高分子有聚乙二醇(polyethylene glycol, PEG)、聚L-赖氨酸、聚(苯乙烯-马来酸酐)、聚(环己烷-1,4-丙酮二亚甲基缩酮)、氯化聚苯乙烯树脂、聚乳酸和一些嵌段共聚物,其抗氧化活性与金属配体有关,是一类潜在的抗癌药物。
Superoxide dismutases (SOD) is a kind of typical metalloenzymes. It has been paid much attention for its important role in life activities, such as maintaining the dynamic equilibrium of the superoxide anion radicals in vivo. At present, the simulation of SOD has been developed from small molecule compounds as active center to system simulation, in which active center was combined into polymer environment. This paper reviews the progress of SOD mimics in polymers perspective. Based on studying simulation strategies, we can get new ideas for designing and exploiting a new-type biocompatible and high reactive antioxidants. Natural polymer includes proteins and peptides, polysaccharides, molecular aggragates. Recently, steady natural proteins and gene recombined proteins or peptides have been used as SOD mimics. Polysaccharides for mimicing SOD include dextran, carboxymethyl cellulose and chitosan. Above macromolecules could conjugate with small molecule compounds with biological activity, such as metalloporphyrins, homonuclear complexes, heteronuclear complexes with new oximes ligands and salen-type metal complexes. After being conjugated, the activity of small molecule compounds had been promoted greatly, while their stability could also be improved. The environment of natural enzymes in vivo can also be simulated by inserting low molecular weight active compounds into molecular aggragates (micelles and liposomes) as the activity and circulation time of SOD mimics could be improved. Some synthetic polymers, such as polyethylene glycol (PEG), poly( L -lysine), poly(styrene-maleic anhydride), poly(cyclohexane-1,4-acetone methylene ketal) chloride, polystyrene resins, polylactic acid and block copolymers, were also used for SOD mimics. The antioxidant activity of obtained polymer grafted metal complexes was influenced by ligands. They are typical candidates of anti-cancer drugs. Contents
1 Introduction
2 Structure and simulation strategy of SOD
2.1 Structure and function of SOD
2.2 Simulation strategy of SOD
3 SOD mimics based on natural polymers
3.1 Proteins and peptides
3.2 Polysaccharides
3.3 Molecular aggregates
4 SOD mimics based on synthetic polymers
5 Summary
superoxide dismutase
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