Synthesis and conformational analysis of hybrid α/β-dipeptides incorporating S-glycosyl-β2,2-amino acids

  1. García-González, I. 1
  2. Mata, L. 1
  3. Corzana, F. 1
  4. Jiménez-Osés, G. 2
  5. Avenoza, A. 1
  6. Busto, J.H. 1
  7. Peregrina, J.M. 1
  1. 1 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

  2. 2 University of California Los Angeles
    info

    University of California Los Angeles

    Los Ángeles, Estados Unidos

    ROR https://ror.org/046rm7j60

Revista:
Chemistry - A European Journal

ISSN: 0947-6539

Año de publicación: 2015

Volumen: 21

Número: 3

Páginas: 1156-1168

Tipo: Artículo

DOI: 10.1002/CHEM.201405318 SCOPUS: 2-s2.0-84920829521 WoS: WOS:000347615200030 GOOGLE SCHOLAR

Otras publicaciones en: Chemistry - A European Journal

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2013/00007/001

Resumen

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.