Advances in analytical technologies detecting and characterizing noncovalent interactions for fragment-based drug discovery

Davoine, Clara; Pochet, Lionel; Fillet, Marianne

doi:10.1016/j.trac.2023.117161

Article (Scientific journals)

Advances in analytical technologies detecting and characterizing noncovalent interactions for fragment-based drug discovery

Davoine, Clara; Pochet, Lionel; Fillet, Marianne

2023 • In TrAC: Trends in Analytical Chemistry, 166, p. 117161

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/313320

DOI
10.1016/j.trac.2023.117161

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Keywords :

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/Unit :

CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
NARILIS - NAmur Research Institute for LIfe Sciences - UNamur

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

Publication date :

September 2023

Journal title :

TrAC: Trends in Analytical Chemistry

ISSN :

0165-9936

eISSN :

1879-3142

Publisher :

Elsevier B.V.

Volume :

166

Pages :

117161

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://api.elsevier.com/content/article/PII:S0165993623002480?httpAccept=text/xml

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique
Fondation Léon Fredericq

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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