Dynamic Combinatorial Chemistry: A New Methodology Comes of Age |
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Authors: | Priska Frei Dr. Rachel Hevey Prof. em. Dr. Beat Ernst |
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Affiliation: | Institute of Molecular Pharmacy, Pharmacenter, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland |
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Abstract: | Dynamic combinatorial chemistry (DCC) has repeatedly proven to be an effective approach to generate directed ligand libraries for macromolecular targets. In the absence of an external stimulus, a dynamic library forms from reversibly reacting building blocks and reaches a stable thermodynamic equilibrium. However, upon addition of a macromolecular host which can bind and stabilize certain components of the library, the equilibrium composition changes and induces an evolution-like selection and enrichment of high-affinity ligands. A valuable application of this so-called target-directed DCC (tdDCC) is the identification of potent ligands for pharmacologically relevant targets. Over time, the term tdDCC has been applied to describe a number of different experimental setups, leading to some ambiguity concerning its definition. This article systematically classifies known procedures for tdDCC and related approaches, with a special focus on the methods used for analysis and evaluation of experiments. |
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Keywords: | drug discovery dynamic combinatorial chemistry host–guest systems supramolecular chemistry target-directed dynamic combinatorial chemistry |
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