Chemical Dimerizers in Three-Hybrid Systems for Small Molecule-Target Protein Profiling.
The identification of the molecular targets and mechanisms underpinning the beneficial or detrimental effects of small-molecule leads and drugs constitutes a crucial aspect of current drug discovery. Over the last two decades, three-hybrid (3H) systems have progressively taken an important position in the armamentarium of small molecule-target protein profiling technologies. Yet, a prerequisite for successful 3H analysis is the availability of appropriate chemical inducers of dimerization. Herein, we present a comprehensive and critical overview of the chemical dimerizers specifically applied in both yeast and mammalian three-hybrid systems for small molecule-target protein profiling within the broader scope of target deconvolution and drug discovery. Furthermore, examples and alternative suggestions for typical components of chemical dimerizers for 3H systems are discussed. As illustrated, more tools have become available that increase the sensitivity and efficiency of 3H-based screening platforms. Hence, it is anticipated that the great potential of 3H systems will further materialize in important contributions to drug discovery.
Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University , 9000 Ghent, Belgium.
Dries J H
DJ
De Clercq
Department of Medical Protein Research, Vlaams Instituut voor Biotechnologie , 9000 Ghent, Belgium.|Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University , 9000 Ghent, Belgium.
Jan
J
Tavernier
Department of Medical Protein Research, Vlaams Instituut voor Biotechnologie , 9000 Ghent, Belgium.|Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University , 9000 Ghent, Belgium.
Sam
S
Lievens
Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University , 9000 Ghent, Belgium.
Serge
S
Van Calenbergh
D000818:Animals; D019281:Dimerization; D055808:Drug Discovery; D006801:Humans; D011506:Proteins / Q000737:chemistry*
D011506:Proteins