Dépôt numérique

Exposing Small-Molecule Nanoentities by a Nuclear Magnetic Resonance Relaxation Assay

Ayotte, Yann; Marando, Victoria; Vaillancourt, Louis; Bouchard, Patricia; Heffron, Gregory; Coote, Paul W.; Larda, Sacha et Laplante, Steven ORCID logoORCID: 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.

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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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