Conformational analysis of sugar–peptide adducts in the solution state by NMR spectroscopy and molecular modelling

Abstract

A combined use of NMR spectroscopy and molecular modelling has enabled insight into conformational features of the novel sugar–peptide adducts 1–3. Cyclic neoglycopeptide 1, having the β-D-glucopyranose moiety which connects terminal parts of the Tyr-Pro-Phe sequence into a 14-membered ring, has been found in a rigid conformation with a sandwich-like arrangement of the proline residue flanked by the tyrosine and the phenylalanine side-chains. However, cyclic Tyr-Pro-Phe-Val-related Amadori compound 2, with an 18-membered glycopeptide ring, has shown more flexibility in the peptide backbone and amino acid side-chains. Nevertheless, mutarotation was obstructed and the 1-deoxy-D-fructofuranose moiety was found in the β configuration exclusively. The analysis of the Amadori compound 3, with an unsubstituted C-terminal of the Tyr-Pro-Phe-Val peptide, has revealed the presence of conformational isomers arising from trans–cis isomerism of the Tyr¹-Pro² peptide bond, while the 1-deoxy-D-fructose has been found in the β-pyranose form. The results presented here point towards peptide sequence-governed overall conformation of the studied neoglycopeptides.