化学学报 ›› 2024, Vol. 82 ›› Issue (6): 629-640.DOI: 10.6023/A24030082 上一篇 下一篇
综述
吕博海a,b, 勾文峰b, 许飞飞b, 李艳丽b, 李祎亮b,*(), 侯文彬b,*()
投稿日期:
2024-03-14
发布日期:
2024-04-02
作者简介:
吕博海, 2022年毕业于天津中医药大学, 同年9月继续攻读中药学硕士研究生. 研究方向为基于化学生物学的靶点发掘和蛋白质的结构、功能对信号通路的过程影响. |
李祎亮, 中国医学科学院放射医学研究所研究员, 天津市“131”创新人才第一层次人才获得者, 北京协和医学院博士生导师. 长期从事新药研发工作, 重点专注于“分子影像”示踪技术与“药物设计”新策略结合, 开展新靶点药物和分子显像剂的研发. 曾参与并主持完成镇痛新药“地佐辛”、术后肠梗阻新药“爱维莫潘”等新药研发, 获得临床批件16项, 新药证书6项. 2018年, 主持承担天津市重大新药“正电子药物制备及其关键技术”平台建设, 2020年, 荣获天津市创新人才推进计划重点领域创新团队负责人. 近5年来, 带领团队陆续开展AND1、CDK19等原创靶点药物和分子显像剂开发, 已在Clin. Transl. Med., Eur. J. Nucl. Med. Mol. Imaging., Eur. J. Med. Chem.等学术期刊杂志发表高水平论文20余篇, 获得授权发明专利22项. |
侯文彬, 中国医学科学院放射医学研究所研究员, 国务院特殊津贴专家、天津市有突出贡献专家和天津市优秀科技工作者, 天津市“131”人才第1层次人选和“131”人才团队负责人. 主要从事天然药物创新药的研究与开发. 先后主持承担国家支撑计划课题1项, 重大新药创制4项, 主持天津市重大科技攻关7项, 获市科技进步奖一、二、三等奖共3项, 滨海新区科技进步一等奖1项. 作为课题负责人主持完成新药研究20余项, 获新药证书2项, 临床批件10项, 包括胡黄连总苷及胶囊、淫羊藿素及其软胶囊获临床批件等, 申请专利24项, 授权10余项, 作为编委编著7部, 发表论文60余篇. |
基金资助:
Bohai Lyua,b, Wenfeng Goub, Feifei Xub, Yanli Lib, Yiliang Lib,*(), Wenbin Houb,*()
Received:
2024-03-14
Published:
2024-04-02
Contact:
* E-mail: Supported by:
文章分享
随着越来越多的活性有效成分被发现, 探寻这些有效成分的药理作用机制, 鉴定它们有效靶点的需求逐渐增加. 化学生物学作为近年来新发展的一门交叉学科, 是承担此项任务的最佳选择. 其中多种无标记蛋白质分析方法通过研究活性分子化合物与蛋白质相互作用, 从而影响蛋白的化学物理性质, 为药物研发提供新的思路. 这些方法通过检测活性化合物对蛋白质的热稳定性、酶敏感性和分子结构引起的改变, 以及结合光谱、质谱分析等相关技术, 来评估活性化合物的选择性和作用范围, 减少脱靶风险. 总结了多种适用于靶点鉴定的无标记蛋白质分析方法, 对药物的靶点发现具有参考意义.
吕博海, 勾文峰, 许飞飞, 李艳丽, 李祎亮, 侯文彬. 适用于活性化合物靶点鉴定的无标记蛋白质分析方法[J]. 化学学报, 2024, 82(6): 629-640.
Bohai Lyu, Wenfeng Gou, Feifei Xu, Yanli Li, Yiliang Li, Wenbin Hou. Label-free Protein Analysis Methods for Active Compound Targets Identification[J]. Acta Chimica Sinica, 2024, 82(6): 629-640.
方法 | 化合物 | 靶点蛋白 | 参考文献 |
---|---|---|---|
药物亲和力反应靶点稳定性(DARTS) | Bruceine D (BD) | Inhibitor of β-catenin/T-cell factor (ICAT) | [ |
DIA-DARTS | Azelastine | ADP ribosylation factor 1 (ARF1) | [ |
氧化速率蛋白稳定性(SPROX) | NAB5 | RAB1A, member RAS oncogene family (RAB1A) | [ |
iTRAQ- SPROX SILAC-SPROX PAB-SPROX | Tamoxifen (TAM) N-desmethyl tamoxifen (NDT) | Y-box binding protein 1 (YBX1) | [ |
氢氘交换质谱(HDX-MS) | GSK2830371 | Protein phosphatase, Mg2+/Mn2+ dependent 1D (PPM1D) | [ |
AZ1-4 | Phosphatidylinositide 3-kinase γ (PI3Kγ) | [ | |
表面等离子共振法(SPR) | GA-1 | Protein disulfide isomerase family a member 3 (PDIA3) | [ |
Tanshinone I (tan i) | Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) | [ | |
生物膜干涉技术(BLI) | LFS-1107 | Chromosome region maintenance 1 (CRM1) | [ |
AVG-233 | RNA-dependent RNA polymerase RdRp (RdRP) | [ | |
圆二色谱法(CD) | PGA-g-Chol | Human serum albumin (HAS) | [ |
Glycyrrhetinic acid (GA) | HRas proto-oncogene, GTPase (HRAS) | [ | |
饱和转移差核磁共振分析(STD NMR) | NSC622608 | V-domain Ig suppressor of T-cell activation (VISTA) | [ |
Gold-1 a | Heat shock protein 60 (HSP60) | [ |
方法 | 化合物 | 靶点蛋白 | 参考文献 |
---|---|---|---|
药物亲和力反应靶点稳定性(DARTS) | Bruceine D (BD) | Inhibitor of β-catenin/T-cell factor (ICAT) | [ |
DIA-DARTS | Azelastine | ADP ribosylation factor 1 (ARF1) | [ |
氧化速率蛋白稳定性(SPROX) | NAB5 | RAB1A, member RAS oncogene family (RAB1A) | [ |
iTRAQ- SPROX SILAC-SPROX PAB-SPROX | Tamoxifen (TAM) N-desmethyl tamoxifen (NDT) | Y-box binding protein 1 (YBX1) | [ |
氢氘交换质谱(HDX-MS) | GSK2830371 | Protein phosphatase, Mg2+/Mn2+ dependent 1D (PPM1D) | [ |
AZ1-4 | Phosphatidylinositide 3-kinase γ (PI3Kγ) | [ | |
表面等离子共振法(SPR) | GA-1 | Protein disulfide isomerase family a member 3 (PDIA3) | [ |
Tanshinone I (tan i) | Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) | [ | |
生物膜干涉技术(BLI) | LFS-1107 | Chromosome region maintenance 1 (CRM1) | [ |
AVG-233 | RNA-dependent RNA polymerase RdRp (RdRP) | [ | |
圆二色谱法(CD) | PGA-g-Chol | Human serum albumin (HAS) | [ |
Glycyrrhetinic acid (GA) | HRas proto-oncogene, GTPase (HRAS) | [ | |
饱和转移差核磁共振分析(STD NMR) | NSC622608 | V-domain Ig suppressor of T-cell activation (VISTA) | [ |
Gold-1 a | Heat shock protein 60 (HSP60) | [ |
方法 | 化合物 | 靶点蛋白 | 参考文献 |
---|---|---|---|
细胞热漂移测定(CETSA) | Elaiophylin | Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) | [ |
MEHP | Hydroxyacyl-CoA dehydrogenase (HADH) Hydroxysteroid 17-beta dehydrogenase 10 (HSD17B10) | [ | |
热蛋白质组分析(TPP) | Kurarinone | Soluble epoxide hydrolase (sEH) | [ |
Napabucasin | Sirtuin 1 (SIRT1) Chromobox 5 (CBX5) Bardet-Biedl syndrome 7 (BBS7) | [ | |
微量热泳动(MST) | 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) | Voltage dependent anion channel 1 (VDAC1) | [ |
Ruscogenin (Rus) | Myosin heavy-chain IIA (NMMHC IIA) | [ | |
等温滴定量热法(ITC) | Naringia | 14-3-3e | [ |
Lumefantrine | Fli-1 proto-oncogene, ETS transcription factor (FLI1) | [ | |
微量差示扫描荧光法(NanoDSF) | F2050 F1787 | Tetrameric lactate dehydrogenases (LDHs) | [ |
Auranofin Tenatoprazole Omapatrilat | Glutathione peroxidase 1 (GPX1) | [ | |
VU0661013 | Glutathione peroxidase 4 (GPX4) |
方法 | 化合物 | 靶点蛋白 | 参考文献 |
---|---|---|---|
细胞热漂移测定(CETSA) | Elaiophylin | Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) | [ |
MEHP | Hydroxyacyl-CoA dehydrogenase (HADH) Hydroxysteroid 17-beta dehydrogenase 10 (HSD17B10) | [ | |
热蛋白质组分析(TPP) | Kurarinone | Soluble epoxide hydrolase (sEH) | [ |
Napabucasin | Sirtuin 1 (SIRT1) Chromobox 5 (CBX5) Bardet-Biedl syndrome 7 (BBS7) | [ | |
微量热泳动(MST) | 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) | Voltage dependent anion channel 1 (VDAC1) | [ |
Ruscogenin (Rus) | Myosin heavy-chain IIA (NMMHC IIA) | [ | |
等温滴定量热法(ITC) | Naringia | 14-3-3e | [ |
Lumefantrine | Fli-1 proto-oncogene, ETS transcription factor (FLI1) | [ | |
微量差示扫描荧光法(NanoDSF) | F2050 F1787 | Tetrameric lactate dehydrogenases (LDHs) | [ |
Auranofin Tenatoprazole Omapatrilat | Glutathione peroxidase 1 (GPX1) | [ | |
VU0661013 | Glutathione peroxidase 4 (GPX4) |
方法 | 化合物 | 靶点蛋白 | 参考文献 |
---|---|---|---|
荧光关联光谱/荧光互相关光谱 (FCS/FCCS) | RGG sequence | G4s | [ |
c-myc mRNA probe | Coding region determinant-binding protein (CRD-BP) | [ | |
荧光偏振技术(FP) | 8-N-benzyladenosine compounds 1 and 2 | Heat shock protein 72 (HSP72) | [ |
N-Alkylcyclophellitol aziridines | Glucosylceramidase Beta 2 (GBA2) | [ | |
基于相分离的蛋白质相互作用报告 (SPPIER)/蛋白水解酶活性报告的 相分离(SPARK) | Isoprenaline H89 | Protein kinase A (PKA) Forkhead-associated domain 1 (FHA1) | [ |
Neocarzinostatin (NCS) SS-55933 | FHA1 | [ | |
人类蛋白质微阵列 (human proteome microarrays) | Celastrol | Peroxiredoxin 2 (PRDX2) | [ |
Icarin (ICA) | Peroxiredoxin 3 (PRDX3) | [ |
方法 | 化合物 | 靶点蛋白 | 参考文献 |
---|---|---|---|
荧光关联光谱/荧光互相关光谱 (FCS/FCCS) | RGG sequence | G4s | [ |
c-myc mRNA probe | Coding region determinant-binding protein (CRD-BP) | [ | |
荧光偏振技术(FP) | 8-N-benzyladenosine compounds 1 and 2 | Heat shock protein 72 (HSP72) | [ |
N-Alkylcyclophellitol aziridines | Glucosylceramidase Beta 2 (GBA2) | [ | |
基于相分离的蛋白质相互作用报告 (SPPIER)/蛋白水解酶活性报告的 相分离(SPARK) | Isoprenaline H89 | Protein kinase A (PKA) Forkhead-associated domain 1 (FHA1) | [ |
Neocarzinostatin (NCS) SS-55933 | FHA1 | [ | |
人类蛋白质微阵列 (human proteome microarrays) | Celastrol | Peroxiredoxin 2 (PRDX2) | [ |
Icarin (ICA) | Peroxiredoxin 3 (PRDX3) | [ |
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