Advances of validation of bioactive small molecule targets

CHEN Shuqiang; DONG Guoqiang; SHENG Chunquan; ZHANG Wannian

doi:10.3969/j.issn.1006-0111.2016.02.001

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Article Navigation > Journal of Pharmaceutical Practice and Service > 2016 > 34(2): 97-102

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

Advances of validation of bioactive small molecule targets

doi: 10.3969/j.issn.1006-0111.2016.02.001

School of Pharmacy, Second Military Medical University, Shanghai 200433, China

Received Date: 2015-09-07
Rev Recd Date: 2016-01-22

Abstract

With the development of science and the progress of age, medicinal chemistry is not only limited to the lead discovery and the structure-activity relationship studies, but also finding the target of bioactive small molecule drugs has become a tough issue to be solved. The identification and validation of bioactive small molecule targets has become the most critical and difficult task, which plays a decisive role in academic and pharmaceutical research. Herein we summarize the current methods for target identification of small molecules,and mainly discuss about the target identification method by the chemical probes. Recent cases of successful application were also introduced to demonstrate the strategy of probe synthesis and design.
- pulldown,
- small molecule drugs,
- target identification,
- fluorescent probes

References

[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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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

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Advances of validation of bioactive small molecule targets

School of Pharmacy, Second Military Medical University, Shanghai 200433, China

Received Date: 2015-09-07

Rev Recd Date: 2016-01-22

Key words:

Abstract: With the development of science and the progress of age, medicinal chemistry is not only limited to the lead discovery and the structure-activity relationship studies, but also finding the target of bioactive small molecule drugs has become a tough issue to be solved. The identification and validation of bioactive small molecule targets has become the most critical and difficult task, which plays a decisive role in academic and pharmaceutical research. Herein we summarize the current methods for target identification of small molecules,and mainly discuss about the target identification method by the chemical probes. Recent cases of successful application were also introduced to demonstrate the strategy of probe synthesis and design.

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Reference (30)

[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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Advances of validation of bioactive small molecule targets

doi: 10.3969/j.issn.1006-0111.2016.02.001

Abstract

References

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通讯作者: 陈斌, bchen63@163.com

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