Stabilizing unusual conformations in small peptides and glucopeptides using a hydroxylated cyclobutane amino acid

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 (c(4)Ser) residue are reported. This is the first example of a glycopeptide containing a carbohydrate...

Full description

Saved in:
Bibliographic Details
Published inOrganic & biomolecular chemistry Vol. 7; no. 14; pp. 2885 - 2893
Main Authors Fernandez-Tejada, Alberto, Corzana, Francisco, Busto, Jesus H., Avenoza, Alberto, Peregrina, Jesus M.
Format Journal Article
LanguageEnglish
Published CAMBRIDGE Royal Soc Chemistry 01.01.2009
Subjects
Amino Acids
Chemistry
Chemistry, Organic
Cyclobutanes
Glycopeptides - chemical synthesis
Glycopeptides - chemistry
Magnetic Resonance Spectroscopy
Models, Molecular
Physical Sciences
Protein Conformation
Science & Technology
MOLECULAR-DYNAMICS
DESIGN
OLIGOSACCHARIDES
HAIRPIN
GLYCOPROTEINS
SYNTHETIC GLYCOPEPTIDES
STEREOSELECTIVE-SYNTHESIS
MODEL
GLYCOSYLATION
BETA-TURN MODULATION
Online AccessGet full text

Cover

More Information
Summary: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 (c(4)Ser) 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 c(4)Ser-Ala-Ala diamide peptide shows a conformation of two consecutive beta-turn type III structures (the basic structural element of a 3(10) 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-phi conformation.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1477-0520
1477-0539
DOI:10.1039/b907091p