MersV1, Main, Exploration, bibRecord, 000575

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

Identifieur interne : 000575 ( Main/Exploration ); précédent : 000574; suivant : 000576

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

Auteurs : Yann Ayotte [Canada] ; Victoria M. Marando [Canada] ; Louis Vaillancourt [Canada] ; Patricia Bouchard [Canada] ; Gregory Heffron [États-Unis] ; Paul W. Coote [Canada] ; Sacha T. Larda [Canada] ; Steven R. Laplante [Canada]

Source :

Journal of medicinal chemistry [ 1520-4804 ] ; 2019.

RBID : pubmed:31422659

Abstract

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.

DOI: 10.1021/acs.jmedchem.9b00653
PubMed: 31422659

Affiliations:

Canada, États-Unis

Le document en format XML

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<front><div type="abstract" xml:lang="en">Small molecules can self-assemble in aqueous solution into a wide range of nanoentity types and sizes (dimers, <i>n</i>
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Exposing Small-Molecule Nanoentities by a Nuclear Magnetic Resonance Relaxation Assay.

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

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