Stabilizing Unusual Conformations in Small Peptides and Glucopeptides using a Hydroxylated Cyclobutane Amino Acid

  1. Fernández-Tejada, A. 1
  2. Corzana, F. 1
  3. Busto, J.H. 1
  4. Avenoza, A. 1
  5. Peregrina, J.M. 1
  1. 1 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

Revista:
Organic and Biomolecular Chemistry

ISSN: 1477-0520

Año de publicación: 2009

Volumen: 7

Número: 14

Páginas: 2885-2893

Tipo: Artículo

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DOI: 10.1039/B907091P PMID: 19582298 SCOPUS: 2-s2.0-67650456422 WoS: WOS:000267728400009 GOOGLE SCHOLAR

Otras publicaciones en: Organic and Biomolecular Chemistry

Resumen

The synthesis and the conformational study in the solid state and in aqueous solution of a peptide and a glucopeptide containing the non-natural (1S,2S)-1-amino-2-hydroxycyclobutanecarboxylic acid (c4Ser) residue are reported. This is the first example of a glycopeptide containing a carbohydrate moiety linked to an underlying non-natural amino acid residue. The conformational analysis in solution combines NOEs and coupling constants data with Molecular Dynamics (MD) simulations with time-averaged restraints. The study reveals that the c4Ser-Ala-Ala diamide peptide shows a conformation of two consecutive β-turn type III structures (the basic structural element of a 310 helix). However, none of the turns observed in the peptide are present in the derived glucopeptide. The influence of the carbohydrate moiety on the peptide backbone can be explained by means of the existence of two simultaneous hydrogen bonds, between the endocyclic oxygen of the glucose and two amidic protons of the peptide. In addition, the non-natural residue favors the existence of an unusual high energy conformation for the glycosidic linkage, the so-called anti- conformation. © 2009 The Royal Society of Chemistry.