Affinity capillary electrophoresis; Analytical techniques; Biomolecular interaction; DNA-Encoded chemical libraries; Drug discovery; Fragment-based drug discovery; Microscale thermophoresis; Weak affinity chromatography; Analytical technique; Biomolecular interactions; Chemical libraries; DNA-encoded chemical library; Analytical Chemistry; Spectroscopy
Abstract :
[en] Detection and characterization of biomolecular interactions are the backbone of the drug discovery process. One of the most widely used approaches to developing new drugs is the fragment-based drug discovery (FBDD) strategy. The FBDD approach begins with the discovery of low molecular weight chemical fragments that bind weakly to the target of interest. The identified fragments are then combined or optimized into potent drug-like compounds. Despite its advantages over the high-throughput screening approach, its execution can be challenging. The reason is that discovering weak binders and determining how to grow or bind them are difficult. Therefore, intensive research is still underway to develop analytical technologies to detect and characterize weak, non-covalent interactions. The purpose of this article is to comprehensively review the emerging analytical technologies used in FBDD compared with the conventional ones. Particularly, we summarize their principle, advantages, limitations, and potential artifacts. For each emerging technique, we provide practical examples. Accurate detection and characterization of weak interactions are critical for the success of a FBDD project. Hence, knowledge of the features of the different techniques can support the selection and implementation of the project's analytical platform.
Research center :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège [BE] NARILIS - NAmur Research Institute for LIfe Sciences - UNamur [BE]
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Davoine, Clara ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM) ; Namur Medicine & Drug Innovation Center (NAMEDIC – NARILIS), University of Namur, Namur, Belgium
Pochet, Lionel ; Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique ; Namur Medicine & Drug Innovation Center (NAMEDIC – NARILIS), University of Namur, Namur, Belgium
Fillet, Marianne ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Language :
English
Title :
Advances in analytical technologies detecting and characterizing noncovalent interactions for fragment-based drug discovery
F.R.S.-FNRS - Fund for Scientific Research [BE] Fondation Léon Fredericq [BE]
Funding text :
C. D. received funding from the National Fund for Scientific Research (FNRS) [grant number 40000455 ]; and Fondation Léon Frédéricq [grant number 2020-2021-30 -C.F.F]. L. P. received funding from the University of Namur [grant number L. POCHET-12/2021 ]. M. F. received funding from the University of Liège Fonds Spéciaux—Crédits facultaires [grant number 14758 ].
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