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Target Identification for Small Bioactive Molecules: Finding the Needle in the Haystack
Author(s) -
Ziegler Slava,
Pries Verena,
Hedberg Christian,
Waldmann Herbert
Publication year - 2013
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201208749
Subject(s) - haystack , identification (biology) , computational biology , workflow , computer science , small molecule , data science , biochemical engineering , proteomics , nanotechnology , chemistry , biology , artificial intelligence , engineering , biochemistry , botany , materials science , database , gene
Identification and confirmation of bioactive small‐molecule targets is a crucial, often decisive step both in academic and pharmaceutical research. Through the development and availability of several new experimental techniques, target identification is, in principle, feasible, and the number of successful examples steadily grows. However, a generic methodology that can successfully be applied in the majority of the cases has not yet been established. Herein we summarize current methods for target identification of small molecules, primarily for a chemistry audience but also the biological community, for example, the chemist or biologist attempting to identify the target of a given bioactive compound. We describe the most frequently employed experimental approaches for target identification and provide several representative examples illustrating the state‐of‐the‐art. Among the techniques currently available, protein affinity isolation using suitable small‐molecule probes (pulldown) and subsequent mass spectrometric analysis of the isolated proteins appears to be most powerful and most frequently applied. To provide guidance for rapid entry into the field and based on our own experience we propose a typical workflow for target identification, which centers on the application of chemical proteomics as the key step to generate hypotheses for potential target proteins.