Determining the Predominant Conformations of Mortiamides A-D in Solution Using NMR Data and Molecular Modeling Tools.
ACS Omega
; 8(29): 25832-25838, 2023 Jul 25.
Article
in En
| MEDLINE
| ID: mdl-37521620
Macrocyclic peptidomimetics have been seriously contributing to our arsenal of drugs to combat diseases. The search for nature's discoveries led us to mortiamides A-D (found in a novel fungus from Northern Canada), which is a family of cyclic peptides that clearly have demonstrated impressive pharmaceutical potential. This prompted us to learn more about their solution-state properties as these are central for binding to target molecules. Here, we secured and isolated mortiamide 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-bond and through-space) data to confirm the primary structure, and NMR-driven molecular dynamics (MD) simulations suggested that more than one predominant three-dimensional (3D) structure exist in solution. Further steps of MD simulations are consistent with the finding that the backbones of mortiamides A-C also have at least two prominent macrocyclic shapes, but the side-chain structures and dynamics differed significantly. Knowledge of these solution properties can be exploited for drug design and discovery.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Prognostic_studies
Language:
En
Journal:
ACS Omega
Year:
2023
Document type:
Article
Affiliation country:
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