Portal de Periódicos da CAPES

Chemoenzymatic Solution- and Solid-Phase Synthesis of O -Glycopeptides of the Mucin Domain of MAdCAM-1. A General Route to O -LacNAc, O -Sialyl-LacNAc, and O -Sialyl-Lewis-X Peptides

1997; American Chemical Society; Volume: 119; Issue: 38 Linguagem: Inglês

10.1021/ja971383c

1943-2984

Oliver Seitz, Chi‐Huey Wong,

Peptidase Inhibition and Analysis

An efficient and general method for the solid-phase synthesis of glycopeptides containing an O-linked sialyl-Lewis-X (SLex) tetrasaccharide is described. Using a combined chemoenzymatic approach, the first synthesis of an unnatural β-O-linked SLex attached to a partial sequence of the mucin domain of the L-selectin ligand MAdCAM-1, was demonstrated. A resin-bound O-glycoconjugate was synthesized from a new Fmoc-threonine building block which carries an O-unprotected β-linked N-acetylglucoseamine (GlcNAc) moiety. The acid- and base-stable HYCRON-linker enabled the complete removal of all protecting groups on solid phase. Glycosyltransferases were employed to extend the glycan on supported and unsupported O-GlcNAc-octapeptide substrates. The acid- and base-sensitive O-glycopeptides were released under practically neutral conditions, taking advantage of the palladium(0)-catalyzed cleavage of the allylic linkage. Studies toward the selective O-deacetylation of ester-linked glycopeptides possessing O-acetyl-protected carbohydrates are also reported.