摘要
背景:疟疾和其他人类疾病中药物靶点的验证仍然是一个非常困难和费力的过程。在绝大多数情况下,仅在体内抑制蛋白质功能的高度特异性的小分子工具根本就不可用。此外,在分析疟疾途径中使用遗传工具是具有挑战性的。这些问题导致在体内特异性调节假设药物靶标功能的困难。 目标:目前用于识别蛋白质在体内功能的各种方法和技术的“工具箱”仍然非常有限,并且迫切需要扩展。迫切需要新的方法来支持药物发现过程中的目标验证。 方法:寡聚化是将单个蛋白质的多个拷贝自然组装成一个对象,并且该自组装存在于所有蛋白质结构的一半以上。 因此,寡聚化在功能性生物分子的产生中起着核心作用。寡聚化的一个关键特征是最终组件的各个部分之间的低聚界面是高度特异性的。然而,这些界面还没有被系统地探索或利用来解剖体内的生物化学途径。 结果和结论:这个迷你评论将描述抗疟药物工具的当前状态以及潜在的药物疟疾途径。特别关注在药物靶标验证中开发低聚表面的初步努力。作为常规方法的替代方案,蛋白质干扰测定(PIA)可用于体内靶蛋白功能和途径评估的特异性失真。
关键词: 药物靶标验证,体内特异性,疟疾,寡聚化,蛋白质干扰,蛋白质:蛋白质相互作用
Current Drug Targets
Title:Drug Target Validation Methods in Malaria - Protein Interference Assay (PIA) as a Tool for Highly Specific Drug Target Validation
Volume: 18 Issue: 9
关键词: 药物靶标验证,体内特异性,疟疾,寡聚化,蛋白质干扰,蛋白质:蛋白质相互作用
摘要: Background: The validation of drug targets in malaria and other human diseases remains a highly difficult and laborious process. In the vast majority of cases, highly specific small molecule tools to inhibit a proteins function in vivo are simply not available. Additionally, the use of genetic tools in the analysis of malarial pathways is challenging. These issues result in difficulties in specifically modulating a hypothetical drug target’s function in vivo.
Objective: The current “toolbox” of various methods and techniques to identify a protein’s function in vivo remains very limited and there is a pressing need for expansion. New approaches are urgently required to support target validation in the drug discovery process. Method: Oligomerisation is the natural assembly of multiple copies of a single protein into one object and this self-assembly is present in more than half of all protein structures. Thus, oligomerisation plays a central role in the generation of functional biomolecules. A key feature of oligomerisation is that the oligomeric interfaces between the individual parts of the final assembly are highly specific. However, these interfaces have not yet been systematically explored or exploited to dissect biochemical pathways in vivo. Results and Conclusion: This mini review will describe the current state of the antimalarial toolset as well as the potentially druggable malarial pathways. A specific focus is drawn to the initial efforts to exploit oligomerisation surfaces in drug target validation. As alternative to the conventional methods, Protein Interference Assay (PIA) can be used for specific distortion of the target protein function and pathway assessment in vivo.Export Options
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Cite this article as:
Drug Target Validation Methods in Malaria - Protein Interference Assay (PIA) as a Tool for Highly Specific Drug Target Validation, Current Drug Targets 2017; 18 (9) . https://dx.doi.org/10.2174/1389450117666160201115003
DOI https://dx.doi.org/10.2174/1389450117666160201115003 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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