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

    GRID grid.119021.a

Journal:
Organic and Biomolecular Chemistry

ISSN: 1477-0520

Year of publication: 2009

Volume: 7

Issue: 14

Pages: 2885-2893

Type: Article

Export: RIS
DOI: 10.1039/b907091p PMID: 19582298 SCOPUS: 2-s2.0-67650456422 WoS: 000267728400009 GOOGLE SCHOLAR

Metrics

Cited by

  • Scopus Cited by: 12 (12-06-2021)

Journal Citation Reports

  • Year 2009
  • Journal Impact Factor: 3.762
  • Best Quartile: Q1
  • Area: CHEMISTRY, ORGANIC Quartile: Q1 Rank in area: 10/57 (Ranking edition: SCIE)

SCImago Journal Rank

  • Year 2009
  • SJR Journal Impact: 1.868
  • Best Quartile: Q1
  • Area: Biochemistry Quartile: Q1 Rank in area: 64/366
  • Area: Organic Chemistry Quartile: Q1 Rank in area: 22/169
  • Area: Physical and Theoretical Chemistry Quartile: Q1 Rank in area: 23/160

Abstract

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.