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应中央军委要求,2022年9月起,《药学实践杂志》将更名为《药学实践与服务》,双月刊,正文96页;2023年1月起,拟出版月刊,正文64页,数据库收录情况与原《药学实践杂志》相同。欢迎作者踊跃投稿!

活性小分子化合物靶点验证方法的研究进展

陈树强 董国强 盛春泉 张万年

陈树强, 董国强, 盛春泉, 张万年. 活性小分子化合物靶点验证方法的研究进展[J]. 药学实践与服务, 2016, 34(2): 97-102. doi: 10.3969/j.issn.1006-0111.2016.02.001
引用本文: 陈树强, 董国强, 盛春泉, 张万年. 活性小分子化合物靶点验证方法的研究进展[J]. 药学实践与服务, 2016, 34(2): 97-102. doi: 10.3969/j.issn.1006-0111.2016.02.001
CHEN Shuqiang, DONG Guoqiang, SHENG Chunquan, ZHANG Wannian. Advances of validation of bioactive small molecule targets[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(2): 97-102. doi: 10.3969/j.issn.1006-0111.2016.02.001
Citation: CHEN Shuqiang, DONG Guoqiang, SHENG Chunquan, ZHANG Wannian. Advances of validation of bioactive small molecule targets[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(2): 97-102. doi: 10.3969/j.issn.1006-0111.2016.02.001

活性小分子化合物靶点验证方法的研究进展

doi: 10.3969/j.issn.1006-0111.2016.02.001
基金项目: 国家自然科学基金(81373278)

Advances of validation of bioactive small molecule targets

  • 摘要: 随着科学的发展和时代的进步,药物化学的研究不仅仅局限于先导化合物的发现及其构效关系的研究,一些小分子药物靶点的确认正逐渐成为阻碍药物化学发展的瓶颈问题。因此,活性小分子化合物靶点的鉴定与确认也成为研究过程中最为关键和艰巨的任务,通常会起到决定性作用。本文简要总结活性小分子化合物靶点验证的现行方法,阐述通过合成探针进行靶标鉴别的手段,介绍探针的设计与合成思想,并列举应用这些方法成功找到靶点的实例。
  • [1] Schuchardt S,Sickmann A. In plant systems biology[M].Netherlands:Springer,2007.
    [2] Duckert H, Pries V, Khedkar V, et al.Natural product-inspired cascade synthesis yields modulators of centrosome integrity[J].Nat Chem Biol, 2012, 8(2):179-184.
    [3] Weerapana E, Speers AE, Cravatt BF.Tandem orthogonal proteolysis-activity-based protein profiling(TOP-ABPP)-a general method for mapping sites of probe modification in proteomes[J].Nat Protoc, 2007, 2(6):1414-1425.
    [4] Speers AE, Cravatt BF.A tandem orthogonal proteolysis strategy for high-content chemical proteomics[J].J Am Chem Soc, 2005, 127(28):10018-10019.
    [5] Sato S, Kwon Y, Kamisuki S,et al.Polyproline-rod approach to isolating protein targets of bioactive small molecules:isolation of a new target of indomethacin[J].J Am Chem Soc,2007, 129(4):873-880.
    [6] Shimizu N, Sugimoto K, Tang J,et al.High-performance affinity beads for identifying drug receptors[J].Nat Biotechnol, 2000, 18(8):877-881.
    [7] Shiyama T, Furuya M, Yamazaki A, et al.Design and synthesis of novel hydrophilic spacers for the reduction of nonspecific binding proteins on affinity resins[J].Bioorg Med Chem, 2004, 12(11):2831-2841.
    [8] Piggott AM, Karuso P.Synthesis of a new hydrophilic onitrobenzyl photocleavable linker suitable for use in chemical proteomics[J].Tetrahedron Lett, 2005, 46(47):8241-8244.
    [9] Koopmans T, Dekker FJ, Martin N.A photocleavable affinity tag for the enrichment of alkyne-modified biomolecules[J].RSC Adv, 2012, 2(6):2244-2246.
    [10] Wirth T, Schmuck K, Tietze LF, et al.Duocarmycin analogues target aldehyde dehydrogenase 1 in lung cancer cells[J]. Angew Chem Int Ed Engl, 2012,51(12):2874-2877.
    [11] Böttcher T, Sieber SA.β-lactones as specific inhibitors of ClpP attenuate the production of extracellular virulence factors of Staphylococcus aureus[J].J Am Chem Soc, 2008, 130(44):14400-14401.
    [12] Wulff JE, Siegrist R, Myers AG.The natural product avrainvillamide binds to the oncoprotein nucleophosmin[J].J Am Chem Soc 2007, 129(46), 14444-14451.
    [13] Tosso PN, Kong Y, Scher L,et al. Synthesis and structure-activity relationship studies of small molecule disruptors of EWS-FLI1 interactions in Ewing's sarcoma[J]. J Med Chem, 2014, 57(24):10290-10303.
    [14] Wang J, Zhang CJ, Chia WN, et al. Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum[J]. Nat Commun, 2015, 6:10111.
    [15] Leuenroth SJ, Okuhara D, Shotwell JD, et al. Triptolide is a traditional Chinese medicine-derived inhibitor of polycystic kidney disease[J]. Proc Natl Acad Sci USA, 2007, 104(11):4389-4394.
    [16] Bao X, Zhao Q, Yang T,et al. A chemical probe for lysine malonylation[J]. Angew Chem Int Ed Engl, 2013, 52(18):4883-4886.
    [17] Tomohiro T, Yamamoto A, Tatsumi Y,et al.[3-(Trifluoromethyl)-3 H-diazirin-3-yl] coumarin as a carbene-generating photocross-linker with masked fluorogenic beacon[J].Chem Commun, 2013, 49(98):11551-11553.
    [18] Jessen KA, English NM, Yu WJ, et al. The discovery and mechanism of action of novel tumor-selective and apoptosis-inducing 3, 5-diaryl-1, 2, 4-oxadiazole series using a chemical genetics approach[J].Mol Cancer Ther, 2005, 4(5):761-771.
    [19] Park C, Marqusee S. Pulse proteolysis:a simple method for quantitative determination of protein stability and ligand binding[J]. Nat Methods, 2005, 2(3):207-212.
    [20] Lomenick B, Hao R, Jonai N, et al. Target identification using drug affinity responsive target stability(DARTS)[J]. Proc Natl Acad Sci USA, 2009, 106(51):21984-21989.
    [21] Chan JN, Vuckovic D, Sleno L, et al. Target identification by chromatographic co-elution:monitoring of drug-protein interactions without immobilization or chemical derivatization[J]. Mol Cell Proteomics, 2012, 11(7):M111. 016642.
    [22] Freedland SJ, Seligson DB, Liu AY, et al. Loss of CD10(neutral endopeptidase) is a frequent and early event in human prostate cancer[J]. Prostate, 2003, 55(1):71-80.
    [23] Keiser MJ, Roth BL, Armbruster BN, et al. Relating protein pharmacology by ligand chemistry[J]. Nat Biotechnol, 2007, 25(2):197-206.
    [24] Keiser MJ, Setola V, Irwin JJ, et al. Predicting new molecular targets for known drugs[J].Nature, 2009, 462(7270):175-181.
    [25] Peters JU, Schnider P, Mattei P, et al. Pharmacological promiscuity:dependence on compound properties and target specificity in a set of recent Roche compounds[J]. Chem Med Chem, 2009, 4(4):680-686.
    [26] Li G, Liu Y, Liu Y, et al. Photoaffinity labeling of small-molecule-binding proteins by DNA-templated chemistry[J]. Angew Chem Int Ed Engl, 2013, 52(36):9544-9549.
    [27] Gould-Rothberg BE, Sundseth SS, DiPippo VA, et al. The characterization of PPAR alpha ligand drug action in an in vivo model by comprehensive differential gene expression profiling[J]. Funct Integr Genomics, 2001, 1(5):294-304.
    [28] Kim S, LaMontagne K, Sabio M, et al. Depletion of methionine aminopeptidase 2 does not alter cell response to fumagillin or bengamides[J]. Cancer Res, 2004, 64(9):2984-2987.
    [29] Henzel WJ, Watanabe C, Stults JT. Protein identification:the origins of peptide mass fingerprinting[J]. J Am Soc Mass Spectrom, 2003, 14(9):931-942.
    [30] Kramer R, Cohen D. Functional genomics to new drug targets[J]. Nat Rev Drug Discov, 2004, 3(11):965-972.
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  • 收稿日期:  2015-09-07
  • 修回日期:  2016-01-22

活性小分子化合物靶点验证方法的研究进展

doi: 10.3969/j.issn.1006-0111.2016.02.001
    基金项目:  国家自然科学基金(81373278)

摘要: 随着科学的发展和时代的进步,药物化学的研究不仅仅局限于先导化合物的发现及其构效关系的研究,一些小分子药物靶点的确认正逐渐成为阻碍药物化学发展的瓶颈问题。因此,活性小分子化合物靶点的鉴定与确认也成为研究过程中最为关键和艰巨的任务,通常会起到决定性作用。本文简要总结活性小分子化合物靶点验证的现行方法,阐述通过合成探针进行靶标鉴别的手段,介绍探针的设计与合成思想,并列举应用这些方法成功找到靶点的实例。

English Abstract

陈树强, 董国强, 盛春泉, 张万年. 活性小分子化合物靶点验证方法的研究进展[J]. 药学实践与服务, 2016, 34(2): 97-102. doi: 10.3969/j.issn.1006-0111.2016.02.001
引用本文: 陈树强, 董国强, 盛春泉, 张万年. 活性小分子化合物靶点验证方法的研究进展[J]. 药学实践与服务, 2016, 34(2): 97-102. doi: 10.3969/j.issn.1006-0111.2016.02.001
CHEN Shuqiang, DONG Guoqiang, SHENG Chunquan, ZHANG Wannian. Advances of validation of bioactive small molecule targets[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(2): 97-102. doi: 10.3969/j.issn.1006-0111.2016.02.001
Citation: CHEN Shuqiang, DONG Guoqiang, SHENG Chunquan, ZHANG Wannian. Advances of validation of bioactive small molecule targets[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(2): 97-102. doi: 10.3969/j.issn.1006-0111.2016.02.001
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