Premium
Dynamics and Hydration Properties of Small Antifreeze‐Like Glycopeptides Containing Non‐Natural Amino Acids
Author(s) -
Corzana Francisco,
Busto Jesús H.,
García de Luis Marisa,
FernándezTejada Alberto,
Rodríguez Fernando,
JiménezBarbero Jesús,
Avenoza Alberto,
Peregrina Jesús M.
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201000375
Subject(s) - chemistry , glycopeptide , amino acid , peptide , antifreeze , random coil , molecule , stereochemistry , moiety , molecular dynamics , threonine , organic chemistry , computational chemistry , circular dichroism , biochemistry , serine , enzyme , antibiotics
Abstract Novel studies on the synthesis and conformation in aqueous solution of three antifreeze‐like glycopeptides containing the sequence Xaa(α‐GalNAc)‐Ala‐Ala, with Xaa being threonine (Thr) or the non‐natural amino acids α‐methylserine (MeSer) or α‐methylthreonine (MeThr), are reported. The study has combined NMR experiments with molecular dynamics simulations. Whereas the Thr derivative is rather rigid in solution and exhibits an extended conformation for the backbone, the non‐natural glycopeptides are fairly flexible and show random coil structures for the peptide sequence. On the other hand, only those glycopeptides with a methyl group at Cβ of the underlying amino acid show perpendicular orientation of the sugar with respect to the peptide moiety. This structural feature, together with the rigidity of the Thr‐containing glycopeptide, makes this system unique to structure the water molecules of its first hydration shell. In addition, despite its chemical similarity, the different observed conformational behaviors of all these molecules, as well as the differences in their dynamics and hydration properties, make them suitable systems to shed light on the key factors that govern antifreeze activity.