基于开环聚合的聚氨基酸材料的二级结构效应及调控

Effect and regulation of the secondary structure of synthetic poly(α-amino acid)based on ring-opening polymerization

聚氨基酸是一类蛋白模拟物,近年来在诸多领域都有着广泛的应用.同天然的蛋白质一样,聚氨基酸的主链氢键作用也赋予其丰富的二级结构,而二级结构的调控对材料的功能以及组装等都有着十分重要的意义.本文结合聚氨基酸近几年的最新研究进展,分析了聚氨基酸二级结构的形成机制以及侧基功能化对二级结构的影响,总结了二级结构的影响因素,在此基础上,详细阐述了二级结构的调控方法,并探讨了二级结构的形成对穿膜、基因递送、抗菌性能、自组装行为以及蛋白修饰的影响.

Protein is one of the most important components that constitute the organism.A unique property of protein is the adoption of highly ordered secondary structure formed by hydrogen bond.Poly(α-amino acid)s are protein mimics that also present hydrogen bonds in the backbone and similarly adopt secondary structure(e.g.,α-helix andβ-sheet).In addition,poly(α-amino acid)s usually possess desired biocompatibility and biodegradability.Therefore,they have demonstrated extensive utilities in the biological fields.In this review,we firstly introduced the formation mechanism of ordered secondary structure of poly(α-amino acid)s.In general,α-helix exhibits rigid rod-like structure due to the intramolecular hydrogen bonds,whileβ-sheet structure is mainly formed based on the intermolecular hydrogen bonds.The polymerization degree of poly(α-amino acid)s that formβ-sheet is often lower than that of poly(α-amino acid)s withα-helix structure.Besides,the formation of the random coil structure is often due to the distortion of the backbone.Then,we discussed the impact of sidechain functionalization on the secondary structure and introduced the existing approaches in modulating the secondary structure,such as controlling the electrostatic interaction,polarity,and hydrogen bonds.By maintaining a separation distance of more than 11σ-bond between the backbone and side charged groups,the poly(α-amino acid)could adoptα-helical structure due to the diminished interference with the backbone hydrogen bonds.The electrostatic interaction among the side chains disturbs the hydrogen bonding,thereby destabilizing theα-helical structure.For instance,the conformation of light-responsive helical poly(α-amino acid)s can transform into random coil due to side-chain electrostatic attraction after irradiation,while random coil-to-helix transition of zwitterionic poly(α-amino acid)s was achieved via elimination of the side-chain electrostatic interaction in response to phosphatase or acidic p H.In addition,the increased polarity of the side chains of polycysteine and poly(homocysteine)derivatives upon oxidation can also realize the order-order and orderdisorder transition of the secondary structure.Moreover,the conformation of poly(α-amino acid)s with triazole groups in the side chains can be transformed from random coil toα-helix when the p H value is decreased,mainly due to the change in the side-chain hydrogen bond pattern.We further summarized the impact of secondary structure on the bio-applications of poly(α-amino acid)s,including cell penetration,gene delivery,anti-microbial therapy,self-assembly,and protein modification.Normally,α-helical conformation features strong membrane penetration and thusα-helical poly(α-amino acid)s can mediate effective gene transfection.p H-responsive,coil-helix transitional poly(α-amino acid)s can allow helix formation in the acidic endolysosomes to specifically penetrate endolysosomal membranes,while light-triggered distortion of the helix at the post-transfection state can diminish the long-term materials toxicity.α-Helical poly(α-amino acid)s with well-tailored structure can also enable potent anti-microbial efficiency by disruption bacterial membranes,and conformation transitionable poly(α-amino acid)s can mediate potent yet selective killing of bacteria upon coil-to-helix transition in response to over-produced phosphatases in infected sites or acidic p H in the stomach.In addition,the secondary structure also has a huge impact on the self-assembly behavior of poly(α-amino acid)s or the pharmacological properties of protein drugs modified with poly(α-amino acid)s.Therefore,the research on the secondary structure and function of poly(α-amino acid)s renders great inspiration for its further application.