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Conformational Effects of the Non-natural α-Methylserine on Small Peptides and Glycopeptides

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posted on 2009-12-18, 00:00 authored by Alberto Fernández-Tejada, Francisco Corzana, Jesús H. Busto, Alberto Avenoza, Jesús M. Peregrina
The synthesis and the conformational analysis in aqueous solution of a peptide and a glycopeptide containing the sequence threonine-alanine-alanine (Thr-Ala-Ala) are reported. Furthermore, the threonine residue has been replaced by the quaternary amino acid α-methylserine (MeSer) and their corresponding non-natural peptide and glycopeptide are also studied. The conformational analysis in aqueous solution combines NOEs and coupling constants data with Molecular Dynamics (MD) simulations with time-averaged restraints. The study reveals that the β-O-glycosylation produces a remarkable and completely different effect on the backbone of the peptide derived from Thr and MeSer. In the former, the β-O-glycosylation is responsible for the experimentally observed shift from extended conformations (peptide) to folded ones (glycopeptide). In contrast, the β-O-glycosylation of the MeSer-containing peptide, which clearly shows two main conformations in aqueous solution [extended ones (70%) and β-turn (30%)], causes a high degree of flexibility for the backbone.

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