Labeling and functionalizing amphipols for biological applications.
Labeling and functionalizing amphipols for biological applications.
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用于生物应用的两性聚合物的标记和功能化。
DOI：
10.1007/s00232-014-9655-y
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Giusti,Fabrice
中科院分区：
文献类型：
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作者：
LeBon,Christel;Popot,Jean-Luc;Giusti,Fabrice
Amphipols（APols）是作为用于处理水溶液中的膜蛋白（MP）的去污剂的替代物而开发的短的两亲聚合物。MP通常在用APOL捕获后比在洗涤剂溶液中稳定得多。迄今为止特征最好的APol称为A8-35，是用辛胺和异丙胺随机衍生的短链聚丙烯酸钠的混合物。它的溶液性质已被详细研究，并已被广泛用于MP的生物化学和生物物理研究。APOL的吸引人的特性之一是，它是相对容易标记它们，同位素或以其他方式，而不影响其物理化学性质。此外，可以混合几种不同改性的APol，以最简单的可能方式实现MP/APol复合物的多重官能化。标记或加标签的APols被用于研究APols的溶液性质、它们的混溶性、它们注射到活生物体中时的生物分布、它们与MP的结合以及MP/APol复合物的组成、结构和动力学，检查表面活性剂的交换在MP的表面，标记MP以跟踪它们在分级实验中的分布或将它们固定化，在生物物理实验中增加APOL和溶剂或MP之间的对比度，改进NMR光谱等。APOL的标记或官能化可以采取各种过程，每种过程在合成和纯化方面都有其特定的限制和优点。本综述概述了A8-35及其同系物的各种衍生物，并讨论了各种合成路线的利弊。
Amphipols (APols) are short amphipathic polymers developed as an alternative to detergents for handling membrane proteins (MPs) in aqueous solution. MPs are, as a rule, much more stable following trapping with APols than they are in detergent solutions. The best-characterized APol to date, called A8-35, is a mixture of short-chain sodium polyacrylates randomly derivatized with octylamine and isopropylamine. Its solution properties have been studied in detail, and it has been used extensively for biochemical and biophysical studies of MPs. One of the attractive characteristics of APols is that it is relatively easy to label them, isotopically or otherwise, without affecting their physical-chemical properties. Furthermore, several variously modified APols can be mixed, achieving multiple functionalization of MP/APol complexes in the easiest possible manner. Labeled or tagged APols are being used to study the solution properties of APols, their miscibility, their biodistribution upon injection into living organisms, their association with MPs and the composition, structure and dynamics of MP/APol complexes, examining the exchange of surfactants at the surface of MPs, labeling MPs to follow their distribution in fractionation experiments or to immobilize them, increasing the contrast between APols and solvent or MPs in biophysical experiments, improving NMR spectra, etc. Labeling or functionalization of APols can take various courses, each of which has its specific constraints and advantages regarding both synthesis and purification. The present review offers an overview of the various derivatives of A8-35 and its congeners that have been developed in our laboratory and discusses the pros and cons of various synthetic routes.