Crystal structure of a fully protected beta-O-galactosylated tripeptide

The crystal structure of the fully protected glycotripeptide N-benzyloxycrbonyl-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-L-threonyl-alpha-aminoisobutyryl-alpha-aminoisobutyric acid tert-butyl ester [Z-(beta-D-GalAc(4))-L-Thr-Aib-Aib-OtBu] has been determined by X-ray diffraction. The peptide backbone is fully extended at Thr(1), left-handed helical at Aib(2), while it is right-handed helical at Aib(3). The fully extended conformation at the N-terminal Thr residue is stabilized by an intramolecular H-bond involving the N-I-H and O-l=C-1 groups (intramolecularly H-bonded C-5 conformation). Two additional intramolecular H-bonds are observed, involving the peptide N-H groups of Aib(2) and Aib(3) as the donors, and the pyranosidic O-5 oxygen atom and the carbonyl oxygen atom of the acetoxy group on C-6 of the sugar, respectively, as the acceptors. Owing to the peptide-sugar H-bonds, the peptide backbone is forced to adopt a conformation dramatically different from the beta-bend/3(10)-helical conformation usually observed for Aib-rich peptides. The implications and limitations of these findings on the effect of O-glycosylation on the conformation of natural peptides are briefly outlined. (C) 1999 Elsevier Science Ltd. All rights reserved.