Identification of intracellular targets of small molecular weight chemical compounds using affinity chromatography

Efforts to characterize small molecular weight chemical inhibitors of pharmacological interest tend to identify molecules with high efficiency and selectivity, to meet the two criteria required for the clinical development of a drug: efficacy and harmlessness. Drug candidates are expected to inhibit...

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Bibliographic Details
Published in:Biotechnology journal 2007-01, Vol.2 (1), p.68-75
Main Authors: Guiffant, Damien, Tribouillard, Déborah, Gug, Fabienne, Galons, Hervé, Meijer, Laurent, Blondel, Marc, Bach, Stéphane
Format: Article
Language:English
Subjects:
Affinity chromatography
Biochemistry, Molecular Biology
Biopolymers
Biopolymers - analysis
Biopolymers - chemistry
Chromatography, Affinity
Chromatography, Affinity - methods
Competition assays
Drug Design
Life Sciences
Microchemistry
Microchemistry - methods
Molecular Weight
Pharmaceutical Preparations
Pharmaceutical Preparations - chemistry
Selectivity
Subcellular Fractions
Subcellular Fractions - chemistry
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Summary:Efforts to characterize small molecular weight chemical inhibitors of pharmacological interest tend to identify molecules with high efficiency and selectivity, to meet the two criteria required for the clinical development of a drug: efficacy and harmlessness. Drug candidates are expected to inhibit efficiently the target they have been optimized against (for example, a particular type of protein kinase). These hits are also designed to not interfere (or as little as possible) with the activity of other cellular enzymes/proteins to reduce undesired side effects. Here we discuss the use of immobilized drugs as affinity chromatography matrices to purify and identify their bona fide intracellular targets. This method not only allows the systematic investigation of the selectivity of pharmacological compounds but also the anticipation of their putative adverse effects.
ISSN:1860-6768
1860-7314
DOI:10.1002/biot.200600223