Target identification of biologically active small molecules via in situ methods

Su, Ying; Ge, Jingyan; Zhu, Biwei; Zheng, Yu‐Guo; Zhu, Qing; Yao, Shao Q.

doi:10.1016/j.cbpa.2013.06.005

Cited by 85 publications

(96 citation statements)

References 56 publications

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“…The authors have successfully accomplished the inter-subunit crosslinking of egg-white avidin tetramer with this probe (Hatanaka et al 1994). Over the next two decades, covalent affinity probes have been extensively employed not only in target identification (Adam et al 2002b;Takaoka et al 2006;MacKinnon et al 2007;Ban et al 2010;Koteva et al 2010;Wurdak et al 2010;Eirich et al 2011;Cisar and Cravatt 2012;Park et al 2012;Shi et al 2012;Park et al 2013;Su et al 2013), but also in affinity labeling of proteins (Dorman and Prestwich 2000;Hatanaka and Sadakane 2002;Chen et al 2003;Hosoya et al 2004;Lee et al 2005;Koshi et al 2008; Tanaka et al Tsukiji et al 2009a;Das 2011;Wacker et al 2011;Wang et al 2011;Hayashi and Hamachi 2012;Tamura et al 2012;Vinkenborg et al 2012;Willems et al 2012) and activity-based proteomic profiling (ABPP) (Kozarich 2003;Chan et al 2004;Ballell et al 2005;Evans and Cravatt 2006;Sadaghiani et al 2007;Salisbury and Cravatt 2007;Cravatt et al 2008;Salisbury and Cravatt 2008;Uttamchandani et al 2008;Nomura et al 2010;…”

Section: Covalent Crosslinkingmentioning

confidence: 96%

“…These ''all-in-one'' probes have high potential to reduce the level of non-specific binding in affinity purification. In 2013, the Yao laboratory designed a type of ''minimalist probes'' containing a terminal alkyne, a diazirine crosslinker, and a functional group for conjugation with the small molecule (Li et al 2013c;Su et al 2013). Without the ligand, these probes are only seven atoms long so that they have minimal perturbation on the binding property of the ligand.…”

Section: Minimal and Integrated Affinity Probesmentioning

confidence: 99%

“…(Koteva et al 2010;Eirich et al 2011). We refer the reader to a number of excellent reviews for more specific examples (Burdine and Kodadek 2004;Leslie and Hergenrother 2008;Sato et al 2010;Das et al 2011;Lomenick et al 2011b;Futamura et al 2013;Schenone et al 2013;Su et al 2013;Ziegler et al 2013;Kawatani and Osada 2014).…”

Section: Introductionmentioning

confidence: 98%

“…In principle, one may accomplish a target ID project with any of these methods, but in practice, people have realized an integrated approach, combining multiple strategies and methods are instrumental to success. Details of various target identification strategies and methods, their respective advantages and limitations, and representative examples have been extensively covered by numerous excellent reviews (Lindsay 2003;Burdine and Kodadek 2004;Parsons et al 2004;Hart 2005;Luesch et al 2005;Parsons et al 2006;Boshoff and Dowd 2007;Perlstein et al 2007;Terstappen et al 2007; Leslie and Hergenrother 2008;Sleno and Emili 2008;Bantscheff et al 2009;Rix and Superti-Furga 2009;Bottcher et al 2010;Chan et al 2010;Sato et al 2010;Chidley et al 2011a;Das et al 2011;Lomenick et al 2011b;Raida 2011;Wierzba et al 2011;Cho and Kwon 2012;Cong et al 2012;Sakamoto et al 2012;Futamura et al 2013;Lee and Bogyo 2013;Park et al 2013;Su et al 2013;Sumranjit and Chung 2013;Ziegler et al 2013;Blagg and Workman 2014;Kawatani and Osada 2014). Here we elect to only focus on the classic biochemical method: affinity purification.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Affinity purification in target identification: the specificity challenge

Zheng

2015

Arch. Pharm. Res.

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Since phenotype-based screening directly evaluates capability of small molecules for modulating biology in actual biological systems, it has become an important discover modality in modern pharmaceutical sciences. However, in order to fully elucidate the molecular mechanism underlying the bioactivity of small molecules, identification of their biological targets is an indispensable step. Among the many target identification strategies developed during the past several decades, affinity purification remains to be one of the most important and powerful approaches, as it can directly reveal the physical interactions between small molecules and their biomolecular targets. However, due to the complexity of the proteome and the diversity of small molecule-protein interactions, affinity purification faces the specificity challenge: how to identify the true specific targets from the non-specific background? Focusing on this challenge, in this review, we briefly introduce the history and background of affinity purification, and then we discussed the major technological developments aiming to address this challenge. We have summarized these approaches in two categories: noise reduction and comparative distinction. This review also highlights the importance of choosing an integrated approach combining multiple methods to achieving success in target identification.

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Section: Covalent Crosslinkingmentioning

confidence: 96%

Section: Minimal and Integrated Affinity Probesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Affinity purification in target identification: the specificity challenge

Zheng

2015

Arch. Pharm. Res.

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“…While medicinal chemists have attempted to design drug molecules that interact with single target proteins, most drug molecules suffer from off-target effects, and their binding partners have not been identified. Consequently, the Yao group developed ABPs for known drug molecules to reveal the targets in situ (65,66). They synthesized ABPs with Dasatinib using alkyne and photoactivatable tags; this anti-cancer drug molecule targets protein kinases.…”

Section: Discoveries Of Specific Protein-small Molecule Protein-protmentioning

confidence: 99%

Small-molecule probes elucidate global enzyme activity in a proteomic context

Lee¹,

Yoo²,

Yoon³

2014

BMB Reports

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The recent dramatic improvements in high-resolution mass spectrometry (MS) have revolutionized the speed and scope of proteomic studies. Conventional MS-based proteomics methodologies allow global protein profiling based on expression levels. Although these techniques are promising, there are numerous biological activities yet to be unveiled, such as the dynamic regulation of enzyme activity. Chemical proteomics is an emerging field that extends these types proteomic profiling. In particular, activity-based protein profiling (ABPP) utilizes small-molecule probes to monitor enzyme activity directly in living intact subjects. In this mini-review, we summarize the unique roles of smallmolecule probes in proteomics studies and highlight some recent examples in which this principle has been applied. [BMB Reports 2014; 47(3): 149-157]

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Vacuolin‐1 inhibits autophagy by impairing lysosomal maturation via PIKfyve inhibition

et al. 2016

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Lysosomal protein degradation via autophagy strictly regulates cellular protein homoeostasis. Herein we performed high-content screening to identify compounds that inhibit autophagy pathways. We obtained 11 hit compounds and performed cluster analysis using cellular morphological information. Vacuolin-1, which induces the formation of giant vacuoles and is a target unknown compound, clustered with the known PIKfyve inhibitor YM201636. We further confirmed that vacuolin-1 is a potent PIKfyve inhibitor, and we finally concluded that PIKfyve inhibitors are novel chemical tools for regulating autophagy.

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Target identification of biologically active small molecules via in situ methods

Cited by 85 publications

References 56 publications

Affinity purification in target identification: the specificity challenge

Affinity purification in target identification: the specificity challenge

Small-molecule probes elucidate global enzyme activity in a proteomic context

Vacuolin‐1 inhibits autophagy by impairing lysosomal maturation via PIKfyve inhibition

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