活性蛋白质表达谱(activity-based protein profiling,ABPP)分析技术是功能蛋白质组学的一种策略,属于化学蛋白质组学的一部分.它借助化学小分子从功能角度直接切入蛋白质组的研究,能够直接对蛋白质组中感兴趣的靶酶蛋白的活性进行检测...活性蛋白质表达谱(activity-based protein profiling,ABPP)分析技术是功能蛋白质组学的一种策略,属于化学蛋白质组学的一部分.它借助化学小分子从功能角度直接切入蛋白质组的研究,能够直接对蛋白质组中感兴趣的靶酶蛋白的活性进行检测,为药物的发现提供强有力的支持.因此,ABPP技术被认为是基于功能的新一代蛋白质组学技术.随着ABPP分析技术和方法的不断成熟,其应用领域也不断扩展.最近一系列研究表明,今后ABPP分析技术可能成为病毒学研究的又一重要武器.本文综述了ABPP分析技术的基本原理及其在病毒学研究中的应用.展开更多
Most drugs exert pharmacological effects through interaction with their target proteins.Therefore,drug target identification is a crucial step towards the understanding of the mechanism of drug action.It is also imper...Most drugs exert pharmacological effects through interaction with their target proteins.Therefore,drug target identification is a crucial step towards the understanding of the mechanism of drug action.It is also imperative to study the pharmacodynamics of a known drug,with an aim to discover the potentially unrevealed actions and thus refine its future clinical applications.Currently,drug-target identification is either through in vitro affinity chromatography-based approaches or in vivo activity-based protein profiling(ABPP)approaches.However,these approaches generally face difficulties discriminating specific drug targets from non-specific ones.To address this issue,we have come up with a strategy by coupling iTRAQTM(isobaric tags for relative and absolute quantitation)quantitative proteomics approach with clickable ABPP,to specifically and compre hensively identify drug targets in live cells.Using this approach,we identified the protein targets of andrographolide,a natural product with known anti-inflammation and anti-cancer effects,in live cancer cells.The identified target list not only confirmed the known functions of the drug but also revealed its potential novel application as a tumor metastasis inhibitor.We have also used this strategy,combining with a cleavable probe to identify the protein targets of aspirin and its binding sites.Our results revealed the roles of aspirin ininhibition of protein synthesis and induction of autophagy,which have been functionally validated.Our strategy is widely applicable to the identification of protein targets of covalent drugs.展开更多
文摘活性蛋白质表达谱(activity-based protein profiling,ABPP)分析技术是功能蛋白质组学的一种策略,属于化学蛋白质组学的一部分.它借助化学小分子从功能角度直接切入蛋白质组的研究,能够直接对蛋白质组中感兴趣的靶酶蛋白的活性进行检测,为药物的发现提供强有力的支持.因此,ABPP技术被认为是基于功能的新一代蛋白质组学技术.随着ABPP分析技术和方法的不断成熟,其应用领域也不断扩展.最近一系列研究表明,今后ABPP分析技术可能成为病毒学研究的又一重要武器.本文综述了ABPP分析技术的基本原理及其在病毒学研究中的应用.
文摘Most drugs exert pharmacological effects through interaction with their target proteins.Therefore,drug target identification is a crucial step towards the understanding of the mechanism of drug action.It is also imperative to study the pharmacodynamics of a known drug,with an aim to discover the potentially unrevealed actions and thus refine its future clinical applications.Currently,drug-target identification is either through in vitro affinity chromatography-based approaches or in vivo activity-based protein profiling(ABPP)approaches.However,these approaches generally face difficulties discriminating specific drug targets from non-specific ones.To address this issue,we have come up with a strategy by coupling iTRAQTM(isobaric tags for relative and absolute quantitation)quantitative proteomics approach with clickable ABPP,to specifically and compre hensively identify drug targets in live cells.Using this approach,we identified the protein targets of andrographolide,a natural product with known anti-inflammation and anti-cancer effects,in live cancer cells.The identified target list not only confirmed the known functions of the drug but also revealed its potential novel application as a tumor metastasis inhibitor.We have also used this strategy,combining with a cleavable probe to identify the protein targets of aspirin and its binding sites.Our results revealed the roles of aspirin ininhibition of protein synthesis and induction of autophagy,which have been functionally validated.Our strategy is widely applicable to the identification of protein targets of covalent drugs.
