Ayotte, Yann; Marando, Victoria; Vaillancourt, Louis; Bouchard, Patricia; Heffron, Gregory; Coote, Paul W.; Larda, Sacha et Laplante, Steven 
ORCID: https://orcid.org/0000-0003-2835-5789
(2019).
Exposing Small-Molecule Nanoentities by a Nuclear Magnetic Resonance Relaxation Assay
Journal of medicinal chemistry
, vol. 62
, nº 17.
pp. 7885-7896.
DOI: 10.1021/acs.jmedchem.9b00653.
Résumé
Small molecules can self-assemble in aqueous solution into a wide range of nanoentity types and sizes (dimers, n-mers, micelles, colloids, etc.), each having their own unique properties. This has important consequences in the context of drug discovery including issues related to nonspecific binding, off-target effects, and false positives and negatives. Here, we demonstrate the use of the spin-spin relaxation Carr-Purcell-Meiboom-Gill NMR experiment, which is sensitive to molecular tumbling rates and can expose larger aggregate species that have slower rotational correlations. The strategy easily distinguishes lone-tumbling molecules versus nanoentities of various sizes. The technique is highly sensitive to chemical exchange between single-molecule and aggregate states and can therefore be used as a reporter when direct measurement of aggregates is not possible by NMR. Interestingly, we found differences in solution behavior for compounds within structurally related series, demonstrating structure-nanoentity relationships. This practical experiment is a valuable tool to support drug discovery efforts.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 20 juill. 2021 21:23 |
| Dernière modification: | 14 nov. 2022 13:52 |
| URI: | https://espace.inrs.ca/id/eprint/11536 |
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