Conformational effects of the non-natural alpha-methylserine on small peptides and glycopeptides.
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 Furthermore, the threonine residue has been replaced by the quaternary amino acid alpha-methylserine (MeSer) and their corresponding non-natural peptide and glycopeptide are also studied.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 beta-O-glycosylation produces a remarkable and completely different effect on the backbone of the peptide derived from Thr and MeSer. In the former, the beta-O-glycosylation is responsible for the experimentally observed shift from extended conformations (peptide) to folded ones (glycopeptide). In contrast, the beta-O-glycosylation of the MeSer-containing peptide, which clearly shows two main conformations in aqueous solution [extended ones (70%) and beta-turn (30%)], causes a high degree of flexibility for the backbone.
Fernández-Tejada
Alberto
A
Departamento de Química, Universidad de La Rioja, Centro de Investigación en Sintesis Química, Grupo de Sintesis Química de La Rioja, UA-CSIC, 26006 Logroño, Spain.
Corzana
Francisco
F
Busto
Jesús H
JH
Avenoza
Alberto
A
Peregrina
Jesús M
JM
D000409:Alanine / Q000737:chemistry; D000577:Amides / Q000737:chemistry; D000595:Amino Acid Sequence; D006020:Glycopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D006031:Glycosylation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D012694:Serine / Q000031:analogs & derivatives* / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013912:Threonine / Q000737:chemistry; D014867:Water / Q000737:chemistry
D000577:Amides; D006020:Glycopeptides; D010455:Peptides; D012997:Solvents; D014867:Water; D013912:Threonine; C035563:2-methylserine; D012694:Serine; D000409:Alanine