Oligosaccharide-peptide ligation of glycosyl thiolates with dehydropeptides: synthesis of S-linked mucin-related glycopeptide conjugates.
A chemoselective strategy for oligosaccharide-peptide ligation is described in which alpha-thio analogues of mucin-related glycoconjugates can be readily accessed through site-selective conjugate addition of complex oligosaccharide thiolates to dehydroalanine-containing peptides. The efficiency of the ligation is highlighted by the rapid convergent assembly of thio-isosteres of the four tumor-associated carbohydrate antigens, T(N), T, ST(N), and 2,6-ST, as a pair of diastereoisomers at the newly formed cysteine stereocenter. The process proceeds in high yield and with complete retention of the alpha-anomeric configuration.
Galonić
Danica P
DP
Department of Chemistry, University of Illinois, Urbana, IL 61801, USA.
Van Der Donk
Wilfred A
WA
Gin
David Y
DY
D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry; D003545:Cysteine / Q000031:analogs & derivatives; D006020:Glycopeptides / Q000138:chemical synthesis*; D006031:Glycosylation; D009077:Mucins / Q000138:chemical synthesis*; D009844:Oligosaccharides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013862:Thiogalactosides / Q000138:chemical synthesis*
D015295:Antigens, Tumor-Associated, Carbohydrate; D006020:Glycopeptides; D009077:Mucins; D009844:Oligosaccharides; D010455:Peptides; D013438:Sulfhydryl Compounds; D013862:Thiogalactosides; C015102:dehydroalanine; D003545:Cysteine; D000409:Alanine