用分子光开关控制蛋白质功能与时间和细胞/亚细胞维度的空间分辨率。

IF 10.9 1区 医学 Q1 CHEMISTRY, MEDICINAL
Saugata Sahu, Ammathnadu S. Amrutha, Nobuyuki Tamaoki
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引用次数: 0

摘要

利用光开关配体以开关方式控制蛋白质的功能和相关的下游效应是光药理学和药物化学领域的一个活跃研究领域。时间控制赋予了一种特权,即在不永久破坏蛋白质的情况下,确定特定受体在生物事件中的关键作用。此外,光可以选择性地应用于细胞和亚细胞水平的空间分辨率来调节蛋白质功能。时空分辨率使得探测特定受体、受体异构体或特定信号通路成为可能。这种可逆和快速的时空控制对于研究高动态生物过程中的蛋白质功能非常有益,包括但不限于信号转导、神经传递、细胞分裂、免疫反应、蛋白质折叠和蛋白质降解。虽然已经开发出几种光活性配体来有效地控制蛋白质的功能,但文献中关于蛋白质功能具有空间分辨率的报道很少。实现有效的光开关来研究蛋白质功能的主要挑战是有效的合成策略、配体的光稳定性、双向可见光开关能力,最重要的是用光精确控制所需光异构体的局部浓度。活性光异构体的位点特异性定位取决于多种因素,如光开关的性质、两种光异构体的结合亲和力、分子扩散和光照射条件。本文综述了适当的技术和不同因素在实现蛋白质功能的细胞和亚细胞尺寸控制中的作用。讨论了多种策略,以及它们的优点和局限性,以探索这些方法在操纵蛋白质功能方面的巨大潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Controlling Protein Functionalities With Temporal and Cellular/Subcellular Dimensions of Spatial Resolution With Molecular Photoswitches

The use of photoswitchable ligand to control the protein functionalities and related downstream effects in an on-off manner is an active research area in photopharmacology and medicinal chemistry. Temporal control grants a privilege to identify the crucial role of a particular receptor in biological occurrences without destroying the protein permanently. Additionally, light can be applied site-selectively to regulate protein functionality with cellular and sub-cellular levels of spatial resolutions. The spatiotemporal resolution enables the probing of a specific receptor, a receptor isoform, or a particular signalling pathway. This reversible and fast spatiotemporal control is highly beneficial in studying protein functionalities in highly dynamic biological processes, including but not limited to signal transduction, neurotransmission, cell divisions, immune response, protein folding, and protein degradation. Though several light-active ligands have been developed to control protein functionality in an on-off manner efficiently, only a few reports on protein functionality with spatial resolution exist in the literature. Major challenges to achieve efficient photoswitches to study protein functionalities are efficient synthesis strategy, photostability of the ligand, bidirectional visible light switching ability and most importantly precise controlling of the local concentration of desired photoisomer using light. The site-specific localization of the active photoisomer depends on multiple factors like the nature of the photoswitch, the binding affinity of both photoisomers, molecular diffusion and light irradiation conditions. The present review discusses suitable techniques and the role of different factors in achieving cellular and subcellular dimension control in protein functionality. Multiple strategies are discussed, along with their advantages and limitations, to explore the enormous potentiality of these approaches in manipulating protein functionality.

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来源期刊
CiteScore
29.30
自引率
0.00%
发文量
52
审稿时长
2 months
期刊介绍: Medicinal Research Reviews is dedicated to publishing timely and critical reviews, as well as opinion-based articles, covering a broad spectrum of topics related to medicinal research. These contributions are authored by individuals who have made significant advancements in the field. Encompassing a wide range of subjects, suitable topics include, but are not limited to, the underlying pathophysiology of crucial diseases and disease vectors, therapeutic approaches for diverse medical conditions, properties of molecular targets for therapeutic agents, innovative methodologies facilitating therapy discovery, genomics and proteomics, structure-activity correlations of drug series, development of new imaging and diagnostic tools, drug metabolism, drug delivery, and comprehensive examinations of the chemical, pharmacological, pharmacokinetic, pharmacodynamic, and clinical characteristics of significant drugs.
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