Chemical and chemoenzymatic synthesis of glycosyl-amino acids and glycopeptides related to Trypanosoma cruzi mucins.
This study describes the synthesis of the alpha- and beta-linked N-acetyllactosamine (Galp-beta-1,4-GlcNAc; LacNAc) glycosides of threonine (LacNAc-Thr). LacNAc-a-Thr was prepared by direct chemical coupling of a 2-azido-2-deoxy-lactose disaccharide donor to a suitable partially protected threonine unit. In contrast, stepwise chemical generation of beta-linked N-acetylglucosamine followed by enzymatic galactosylation to give LacNAc-beta-Thr proved effective, whereas use of a 2-azido-2-deoxy-lactose donor in acetonitrile failed to give the desired beta-linked disaccharyl glycoside. This study illustrates that it is possible to overcome the inherent stereoselection for 1,2-trans chemical glycosylation with a GlcNAc donor, and that the well-established preference of bovine beta-1,4-galactosyltransferase for beta-linked acceptor substrates can also be overcome. Using this knowledge, short glycopeptide fragments based on T. cruzi mucin sequences, Thr-Thr-[LacNAcThr]-Thr-Thr-Gly, were synthesised. All LacNAc-based compounds outlined were shown to serve as acceptor substrates for sialylation by T. cruzi trans-sialidase.
Campo
Vanessa Leiria
VL
School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich, UK NR4 7TJ.
Carvalho
Ivone
I
Allman
Sarah
S
Davis
Benjamin G
BG
Field
Robert A
RA
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D004789:Enzyme Activation; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D009077:Mucins / Q000737:chemistry*; D009439:Neuraminidase / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D013237:Stereoisomerism; D014349:Trypanosoma cruzi / Q000737:chemistry* / Q000201:enzymology / Q000235:genetics
D000596:Amino Acids; D006020:Glycopeptides; D006023:Glycoproteins; D006027:Glycosides; D009077:Mucins; C069715:trans-sialidase; D009439:Neuraminidase