title: Synthesis and conformational analysis of hybrid α/β-dipeptides incorporating S-glycosyl-β(2,2)-amino acids.
abstract: We synthesized and carried out the conformational analysis of several hybrid dipeptides consisting of an α-amino acid attached to a quaternary glyco-β-amino acid. In particular, we combined a S-glycosylated β(2,2)-amino acid and two different types of α-amino acid, namely, aliphatic (alanine) and aromatic (phenylalanine and tryptophan) in the sequence of hybrid α/β-dipeptides. The key step in the synthesis involved the ring-opening reaction of a chiral cyclic sulfamidate, inserted in the peptidic sequence, with a sulfur-containing nucleophile by using 1-thio-β-D-glucopyranose derivatives. This reaction of glycosylation occurred with inversion of configuration at the quaternary center. The conformational behavior in aqueous solution of the peptide backbone and the glycosidic linkage for all synthesized hybrid glycopeptides was analyzed by using a protocol that combined NMR experiments and molecular dynamics with time-averaged restraints (MD-tar). Interestingly, the presence of the sulfur heteroatom at the quaternary center of the β-amino acid induced θ torsional angles close to 180° (anti). Notably, this value changed to 60° (gauche) when the peptidic sequence displayed aromatic α-amino acids due to the presence of CH-π interactions between the phenyl or indole ring and the methyl groups of the β-amino acid unit.
authors.affiliation: Departamento de Química, Centro de Investigación en Síntesis Química, Universidad de La Rioja, C/Madre de Dios 51, 26006 Logroño, La Rioja (Spain).
authors.forename: Iván
authors.initials: I
authors.lastname: García-González
authors.forename: Lara
authors.initials: L
authors.lastname: Mata
authors.forename: Francisco
authors.initials: F
authors.lastname: Corzana
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Jiménez-Osés
authors.forename: Alberto
authors.initials: A
authors.lastname: Avenoza
authors.forename: Jesús H
authors.initials: JH
authors.lastname: Busto
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Peregrina
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D013451:Sulfonic Acids / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000596:Amino Acids; D004151:Dipeptides; D013451:Sulfonic Acids; C005741:sulfamic acid
keywords: amino acids; glycopeptides; molecular dynamics; nucleophilic substitution; ring-opening reactions