Determining the Predominant Conformations of Mortiamides A-D in Solution Using NMR Data and Molecular Modeling Tools

Franca, Tanos Celmar Costa; Goncalves, Arlan da Silva; Berube, Christopher; Voyer, Normand; Aubry, Norman et Laplante, Steven ORCID: https://orcid.org/0000-0003-2835-5789 (2023). Determining the Predominant Conformations of Mortiamides A-D in Solution Using NMR Data and Molecular Modeling Tools ACS Omega , vol. 8 , nº 29. pp. 25832-25838. DOI: 10.1021/acsomega.3c01206.

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Résumé

Macrocyclic peptidomimetics have been seriously contributingtoour arsenal of drugs to combat diseases. The search for nature'sdiscoveries led us to mortiamides A-D (found in a novel fungusfrom Northern Canada), which is a family of cyclic peptides that clearlyhave demonstrated impressive pharmaceutical potential. This promptedus to learn more about their solution-state properties as these arecentral for binding to target molecules. Here, we secured and isolatedmortiamide D, and then acquired high-resolution nuclear magnetic resonance(NMR) data to learn more about its structure and dynamics attributes.Sets of two-dimensional NMR experiments provided atomic-level (through-bondand through-space) data to confirm the primary structure, and NMR-drivenmolecular dynamics (MD) simulations suggested that more than one predominantthree-dimensional (3D) structure exist in solution. Further stepsof MD simulations are consistent with the finding that the backbonesof mortiamides A-C also have at least two prominent macrocyclicshapes, but the side-chain structures and dynamics differed significantly.Knowledge of these solution properties can be exploited for drug designand discovery.

Type de document:	Article
Mots-clés libres:	-
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	30 déc. 2023 22:28
Dernière modification:	03 févr. 2024 22:36
URI:	https://espace.inrs.ca/id/eprint/13641

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