CAS OpenIR
两亲性氨基酸调控酞菁或金属离子 自组装仿生酶及催化性能研究
韩晶晶
Subtype硕士
Thesis Advisor闫学海
2019-07-01
Degree Grantor中国科学院大学
Degree Discipline生物化工
Keyword仿生酶,自组装,氨基酸,酞菁染料,金属离子
Abstract

天然酶是一种具有三维活性结构的生物大分子催化剂,其在天然催化过程中具有极高的催化效率和底物识别特性。这些优势大力推动了科学家们对仿生酶的研究。酶模拟物可作为一种价格低廉、高效及高稳定性的天然酶替代物。该替代物在有机合成、环境保护中具有重要作用,并可帮助阐明天然酶的催化机制以及了解生物酶在生命起源的进化。仿生酶的设计原则主要是选取其生物酶组分中的关键组分为主体。当前酶模拟物的主要主体为非蛋白源分子。这些主体很大程度上限制了仿生酶的生物体内应用。如何设计催化位点,选择主体分子并将其整合在活性三维结构中,并实现可调控催化是我们面临的一大挑战。自然界中有序的蛋白质分子聚集体主要由分子间相互作用力及配位作用驱动组装形成。受天然酶启发,我们构建了光氧化酶模拟物及金属纳米酶模拟物,进一步推动了新型仿生酶构建及其在催化性能研究。主要工作内容如下:(1)在此,我们设计了基于小分子共组装的光氧化酶纳米囊泡。9-芴基甲氧基羰基-L-组氨酸(Fmoc-His-OH)与酞菁可共组装为纳米囊泡。该仿生酶可灵活调节粒径分布和膜厚度,并具有活性氧物质介导的光敏氧化能力。与单纯的酞菁染料相比,纳米囊泡中的酞菁染料近似于单分子分散,可以增强染料荧光强度及产生单线态氧能力;进一步改善了光敏氧化过程中光催化效率和稳定性。(2)我们提出了通过金属离子配位氨基酸的共组装金属纳米酶。N-(苄氧基羰基)-组氨酰肼(Z-His-NHNH2)可与锌离子灵活配位形成具有可调控粒径和催化活性的纳米酶。基于不同金属浓度构建的纳米级超分子网络可用于模拟水解酶活性;该仿生酶被认为是最简单的金属纳米酶,并具有很强的环境耐受性;可以在未来用作人工药物潜在催化载体。以上工作说明氨基酸可调控酞菁及金属离子形成有效的超分子催化剂作为酶模拟物,并解决了目前选择仿生酶催化主体、构建活性结构以及实现可控催化等难题。所构建的超分子光催化剂能够对理解简单光催化膜系统、水解酶进化路径提供思路;并可应用于未来光敏纳米反应器、人造细胞器及潜在前药递送。;The natural enzyme is a biomacromolecular catalyst with a three-dimensional active structure, which has extremely high catalytic efficiency and substrate recognition characteristics in the natural catalytic process. These advantages of natural enzyme have greatly promoted scientists' research on biomimetic enzymes. Enzyme mimics have the advantages of low cost, high efficiency and high stability and can be used as a natural enzyme alternative. This alternative plays an important role in organic synthesis, environmental protection, helping to elucidate the catalytic mechanisms of natural enzymes and understanding the evolution of biological enzymes in the origin of life. The design principle of the biomimetic enzyme is mainly to select the key components in the biological enzyme component as host. The hosts of current enzyme mimics are non-protein molecules. These non-protein molecules largely limit the application of enzyme mimics in vivo. At the same time, how to design the catalytic sites, select the host molecules and integrate them into the active three-dimensional structure, and realize the controllable catalytic application is one major challenge. Ordered protein molecular aggregates in nature are mainly assembled with the help of intermolecular interactions including coordination. Inspired by naturally occurring enzyme, we constructed photooxidase mimics and the minimal metallo-nanozyme, further promoting the research of catalytic properties of novel enzyme mimics. The main work is as follows:(1) Here, we developed a photooxidase-mimicking nanovesicles based on small molecule co-assembly. 9-Mercaptomethoxycarbonyl-L-histidine (Fmoc-His-OH) and phthalocyanine can be co-assembled into nanovesicles. The biomimetic enzyme has a flexible particle size and film thickness, and an active oxygen species mediated photooxidation capability. Compared to pure phthalocyanine dyes in aqueous solution, phthalocyanine dyes in nanovesicle achieve near-monomolecular dispersion and enhance their fluorescence intensity and ability to produce singlet oxygen. The photocatalytic efficiency and stability in the photosensitive oxidation process are further improved.(2) We proposed a metallo-nanozyme that self-assembles by coordinated amino acids and metal ions. N-(benzyloxycarbonyl)-histidine hydrazide (Z-His-NHNH2) can be flexibly coordinated with zinc to form nanozymes with a tunable particle size and metallo-nanozyme activity. The nano-based supramolecular network based on different metal concentrations mimics the activity of hydrolase, which can be considered as the simplest metallo-nanozyme with good environmental tolerance and can be used as a catalytic carrier for potential artificial prodrugs in future.These work shows that amino acids can regulate phthalocyanine and metal ions to form effective supramolecular catalysts as enzyme mimics. This study solves the problems including the selection of current enzymatic catalytic host, the construction of active structure and the controllable catalysis. The constructed supramolecular photocatalysts can provide ideas for possible evolutionary pathways of simple photocatalytic membrane systems and hydrolases, and can be applied to photosensitive nanoreactors, artificial organelles and potential prodrug delivery in future. 

Language中文
Document Type学位论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/40615
Collection中国科学院过程工程研究所
Recommended Citation
GB/T 7714
韩晶晶. 两亲性氨基酸调控酞菁或金属离子 自组装仿生酶及催化性能研究[D]. 中国科学院大学,2019.
Files in This Item:
File Name/Size DocType Version Access License
两亲性氨基酸调控酞菁或金属离子 自组装仿(3669KB)学位论文 限制开放CC BY-NC-SAApplication Full Text
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[韩晶晶]'s Articles
Baidu academic
Similar articles in Baidu academic
[韩晶晶]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[韩晶晶]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.