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Probing the Conformation-Dependent Preferential Binding of Ethanol to Cationic Glycylalanylglycine in Water/Ethanol by Vibrational and NMR Spectroscopy
Journal article

Probing the Conformation-Dependent Preferential Binding of Ethanol to Cationic Glycylalanylglycine in Water/Ethanol by Vibrational and NMR Spectroscopy

David DiGuiseppi, Bridget Milorey, Gabrielle Lewis, Nina Kubatova, Stefanie Farrell, Harald Schwalbe and Reinhard Schweitzer-Stenner
The journal of physical chemistry. B, v 121(23), pp 5744-5758
15 Jun 2017
PMID: 28530400

Abstract

Chemistry Chemistry, Physical Physical Sciences Science & Technology
The conformational propensity of amino acid residues is determined by an intricate balance of peptide-solvent and solvent-solvent interactions. To explore how the systematic replacement of water by a cosolvent affects the solvation of both the amino acid backbone and side chains, we performed a combined vibrational spectroscopy and NMR study of cationic glycylalanylglycine (GAG) in different ethanol/water mixtures of between 0 and 42 mol percent ethanol. Classical model peptide N'-methylacetamide was used as a reference system to probe solvent-induced spectroscopic changes. The alanine residue of GAG in water is known to exhibit a very high propensity for polyproline II (pPII). Adding up to 30 mol % ethanol at room temperature leads only to minor changes in the Ramachandran distribution of alanine, which mostly changes within the individual conformational subspaces. A further increase in the ethanol fractions leads to a destabilization of pPII and a stabilization of beta-strand conformations. At higher temperatures, different degrees of enthalpyentropy compensations lead to a much stronger influence of ethanol on the peptides conformational distribution. Ethanol-induced changes in chemical shifts and amide I wavenumbers strongly suggest that ethanol replaces water preferentially in the solvation shell of the polar C-terminal peptide group and of the alanine side chain, whereas the N-terminal group remains mostly hydrated. Furthermore, we found that ethanol interacts more strongly with the peptide if the latter adopts beta-strand conformations. This leads to an unusual positive temperature coefficient for the chemical shift of the C-terminal amide proton. Our data suggests a picture in which GAG eventually accumulates at waterethanol interfaces if the ethanol fractions exceed 0.3, which explains why the further addition of ethanol eventually causes self-aggregation and the subsequent formation of a hydrogel.

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Web of Science research areas
Chemistry, Physical
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