Investigating Interaction Dynamics of an Enantioselective Peptide-Catalyzed Acylation Reaction.

Autor: Brauser M; Clemens-Schöpf-Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Peter-Grünberg-Str.16, 64287, Darmstadt, Germany., Petzold K; Biomedicinskt centrum (BMC), Husargatan 3, 752 37, Uppsala, Sweden.; Centre of Excellence for the Chemical Mechanisms of Life, Uppsala University, Husargatan 3, 75237, Uppsala, Sweden.; Science for Life Laboratory, Uppsala Biomedical Centre, Uppsala University, Husargatan 3, 75237, Uppsala, Sweden., Thiele CM; Clemens-Schöpf-Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Peter-Grünberg-Str.16, 64287, Darmstadt, Germany.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Dec 02, pp. e202421062. Date of Electronic Publication: 2024 Dec 02.
DOI: 10.1002/anie.202421062
Abstrakt: Modern nuclear magnetic resonance (NMR) methods like carbon relaxation dispersion in the rotating frame ( 13 C-R 1ρ ) and proton chemical exchange saturation transfer ( 1 H-CEST) are key methods to investigate molecular recognition in biomacromolecules and to detect molecular motions on the μs to s timescale, revealing transient conformational states. Changes in kinetics can be linked to binding, folding, or catalytic events. Here, we investigated whether these methods allow detection of changes in the dynamics of a small, highly selective peptide catalyst during recognition of its enantiomeric substrates. The flexible tetrapeptide Boc-l-(π-Me)-His- A Gly-l-Cha-l-Phe-OMe, used for the monoacetylation of cycloalkane-diols, is probed at natural abundance using 13 C-R 1ρ and 1 H-CEST. Indeed, we detected differences in dynamics of the peptide upon interaction with the diol. Importantly, these differ depending on the enantiomer of the substrate used. These enantiospecific influences of the substrates on the dynamics of the peptide are rationalized using computational techniques. We find that even though one enantiomer reacts faster, as confirmed by reaction monitoring, the other is more tightly bound in DCM (as confirmed by 1 H-saturation transfer difference (STD) measurements). These findings provide insights into the recognition of the substrates and explain the selectivity differences observed between the solvents toluene and DCM.
(© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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