Glycopeptide Synthesis

NMR analysis of human salivary mucin (MUC7) derived O‐linked model glycopeptides: comparison of structural features and carbohydrate–peptide interactions

“…Yet another hurdle in this endeavour is the availability of adequate amounts of suitable glycopeptides due to some unique glitches involved in their preparation. Notably, recent improvements to procure such target glycopeptides via automated solid phase synthetic protocols have provided a great relief for pursuing such structural studies more efficiently (11–13).…”

Carbopeptides: carbohydrates as potential templates for de novo design of protein models

“…The overall strategy requires an aglycon linker which is a hydroxy acid, that does not lactonize easily, and is preferably UV active. There are few reports on the glycosylation of hydroxy acids (17–19), although precedents on the glycosylation of hydroxy amino acids and, for that matter, the synthesis of glycopeptides are voluminous (20–22). From such studies, it is known that O ‐glycosidic linkages appear to be entirely stable to treatment with concentrated TFA in the absence or presence of carbocation scavengers, particularly while the saccharide retains ester protecting groups (23,24).…”

“…From such studies, it is known that O ‐glycosidic linkages appear to be entirely stable to treatment with concentrated TFA in the absence or presence of carbocation scavengers, particularly while the saccharide retains ester protecting groups (23,24). Carbohydrate O ‐acyl groups are in general stable to repeated treatment with piperidine : DMF (1 : 4) or DBU : DMF (1 : 49) required for removal of the N α −9‐fluorenylmethyloxycarbonyl (Fmoc) protecting group for SPPS (22). It is also well‐established that pentafluorophenyl (Pfp) esters survive exposure to equimolar amounts of strong Lewis acids in organic solvents (15,16,25–27), are reasonably stable towards oxygen nucleophiles under weakly acidic and neutral conditions, and can be purified by silica gel chromatography with dry organic solvents (16) or reversed‐phase HPLC with water/acetonitrile mixtures (26); these properties make Pfp a suitable carboxyl‐protecting group for the glycosylation step.…”

“…Carbohydrate O-acyl groups are in general stable to repeated treatment with piperidine : DMF (1 : 4) or DBU : DMF (1 : 49) required for removal of the N a ±9-¯uorenylmethyloxycarbonyl (Fmoc) protecting group for SPPS(22). It is also well-established that penta¯uorophenyl (Pfp) esters survive exposure to equimolar amounts of strong Lewis acids in organic solvents(15,16,25±27), are reasonably stable towards oxygen nucleophiles under weakly acidic and neutral conditions, and can be puri®ed by silica gel chromatography with dry organic solvents(16) or reversedphase HPLC with water/acetonitrile mixtures (26); these properties make Pfp a suitable carboxyl-protecting group for the glycosylation step. Subsequently, Pfp esters are ef®cient acylating agents, especially in the presence of an auxiliary Jensen and Barany .…”

Antitumor Vaccines Based on Synthetic Mucin Glycopeptides

“…Problems with a and b selectivity are more pronounced when larger glycan structures should be coupled to serine/threonine residues within a peptide. Synthesis of O-glycopeptides by Fmoc solid phase peptide synthesis (SPPS) employing glycosylated amino acids is, therefore, the favorable approach (Kunz 1987;Meldal 1994;Kihlberg and Elofsson 1997;Herzner et al 2000). During peptide backbone assembly, the glycosylated amino acid building blocks are commonly protected.…”