用于配体靶蛋白鉴定的溶剂诱导蛋白质沉淀方法的发展与应用OA
Development and Application of Solvent-induced Protein Precipitation Method for Ligand-target Protein Identification
药物通过与靶蛋白结合调控生命活动,解析药物与蛋白相互作用是阐明作用机制、降低毒副作用、克服耐药性及推动新药研发的关键.传统靶标鉴定方法常需对药物进行化学修饰,易干扰天然结合并产生假阳性结果.溶剂诱导蛋白质沉淀法(SIP)无需化学修饰,通过检测配体结合引发的蛋白质稳定性变化实现靶蛋白高通量筛选,具有操作简便、适用性广等优势.近年来,研究人员在SIP基础上发展出溶剂蛋白质组分析(SPP)、溶剂蛋白质组积分溶解度变化(solvent-PISA)、整合溶剂诱导蛋白沉淀方法(iSPP)以及活细胞溶剂诱导部分细胞固定法(SICFA)等一系列衍生方法,显著提升了检测通量与体系适配性.该文系统综述SIP的基本原理、技术演进与优势局限,总结其在肿瘤、帕金森病、抗菌耐药及疟疾等领域的靶标发现与验证应用,为靶标精准鉴定与创新药物开发提供参考.
Drugs regulate biological processes by binding to target proteins.Characterizing drug and protein interactions is therefore critical for elucidating mechanisms of action,reducing toxic side ef-fects,overcoming drug resistance,and advancing novel drug discovery.Conventional target identifi-cation methods often require chemical modification of drugs,which tends to disturb native binding in-teractions and produce false-positive results.Solvent-induced protein precipitation(SIP)is a label-free approach that enables high-throughput drug target screening by detecting protein stabilization in-duced upon ligand binding,offering distinct advantages including simple operation and broad appli-cability.In recent years,researchers have developed a series of SIP-derived methods,including SPP,solvent-PISA,iSPP,and the live-cell in situ technique SICFA,which have greatly improved throughput and system compatibility.This review systematically summarizes the fundamental princi-ples,technological evolution,advantages,and limitations of SIP,and highlights its applications in target discovery and validation across cancer,Parkinson's disease,antimicrobial resistance,malar-ia,and other fields.We aim to provide a useful reference for precise target identification and innova-tive drug development.
张晓磊;叶玉莹;叶明亮
中国科学院大连化学物理研究所,中国科学院分离分析化学重点实验室,辽宁 大连 116023||中国科学院大学,北京 101408中国科学院大连化学物理研究所,中国科学院分离分析化学重点实验室,辽宁 大连 116023||中国科学院大学,北京 101408中国科学院大连化学物理研究所,中国科学院分离分析化学重点实验室,辽宁 大连 116023||中国科学院大学,北京 101408
化学化工
靶标鉴定化学免修饰配体蛋白质组学液相色谱-质谱联用
target protein identificationchemical modification-free ligandproteomicsLC-MS/MS
《分析测试学报》 2026 (8)
1785-1796,12
国家重点研发计划项目(2021YFA1302601)辽宁省自然科学基金面上项目(2024-MSBA-64)
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