Acceptor hydroxyl group mapping for calf thymus alpha-(1-->3)-galactosyltransferase and enzymatic synthesis of alpha-D-Galp-(1-->3)-beta-D-Galp-(1-->4)-beta D-GlcpNAc analogs.
The epitope of the acceptor substrate for alpha-(1-->3)-galactosyltransferase from calf thymus has been mapped by using a series of mono-deoxygenated and mono-O-alkylated Type II (beta-D-Ga1p-(1-->4)-beta-D-G1cpNAc) disaccharides. The 4-OH group of the beta-D-galactopyranosyl residue is a key polar group essential for glycosyl transfer, tolerating neither deoxygenation nor O-alkylation. Substitution at positions 6 and 6' by a variety of polar alkyl substituents was readily tolerated, allowing the preparative enzymatic synthesis of a series of trisaccharide derivatives carrying polar substituents on each of these hydroxyl groups. These new analogs are potential inhibitors of Clostridium difficile toxin A and of a human anti-alpha-Gal antibody.
Sujino
K
K
Department of Chemistry, University of Alberta, Edmonton, Canada.
Malet
C
C
Hindsgaul
O
O
Palcic
M M
MM
D000818:Animals; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000276:immunology; D002240:Carbohydrate Sequence; D002417:Cattle; D016360:Clostridioides difficile / Q000737:chemistry; D000939:Epitopes / Q000737:chemistry*; D005690:Galactose / Q000276:immunology; D005700:Galactosyltransferases / Q000737:chemistry*; D006031:Glycosylation; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis; D013379:Substrate Specificity; D013950:Thymus Gland / Q000201:enzymology*; D014312:Trisaccharides / Q000138:chemical synthesis*
D001427:Bacterial Toxins; D000939:Epitopes; D009844:Oligosaccharides; D014312:Trisaccharides; D005700:Galactosyltransferases; D005690:Galactose