Synthesis and Conformational Analysis of Hybrid α/β‐Dipeptides Incorporating S‐Glycosyl‐β2,2‐Amino Acids |
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| Authors: | Iván García‐González Dr. Lara Mata Dr. Francisco Corzana Dr. Gonzalo Jiménez‐Osés Prof. Alberto Avenoza Dr. Jesús H. Busto Prof. Jesús M. Peregrina |
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| Affiliation: | 1. Departamento de Química, Centro de Investigación en Síntesis Química, Universidad de La Rioja, C/Madre de Dios?51, 26006 Logro?o, La Rioja (Spain);2. Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095‐1569 (USA) |
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| 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 β2,2‐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. |
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| Keywords: | amino acids glycopeptides molecular dynamics nucleophilic substitution ring‐opening reactions |
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