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Synthesis of tumor associated sialyl‐T‐glycopeptides and their immunogenicity
Author(s) -
Komba Shiro,
Werdelin Ole,
Jensen Teis,
Meldal Morten
Publication year - 2000
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/1099-1387(200012)6:12<585::aid-psc274>3.0.co;2-0
Subject(s) - glycopeptide , chemistry , residue (chemistry) , immunogenicity , hydrolysis , solid phase synthesis , sialic acid , combinatorial chemistry , stereochemistry , chromatography , organic chemistry , peptide , antigen , biochemistry , biology , genetics , antibiotics
Abstract Sialyl‐T‐glycopeptides were synthesized by solid‐phase techniques, using a PEGA resin as the solid support. An appropriately protected building block containing α‐Neu5Ac‐(2→3)‐β‐Gal‐(1→3)‐α‐GalN 3 ‐(1→) attached to Fmoc‐Thr/Ser‐OPfp was employed in a solid‐phase glycopeptide assembly of a 10‐mer glycopeptide, using a general Fmoc/OPfp‐ester strategy. Reduction of the azido group of the GalN 3 residue was effected on solid‐phase, using DTT and DBU. After acidolytic cleavage from the resin, the methyl ester of the sialic acid residue and acetyl groups were removed with 30% NaOMe/MeOH in MeOH and water pH 14, at −30°C for 2 h. At this low temperature, the highly basic conditions did not result in any detectable β‐elimination. However, one O‐acetyl group, located at the 2‐position of the Gal was resistant to hydrolysis. To remove this remaining acetyl group, reaction with hydrazine hydrate in CHCl 3 and MeOH at room temperature for 2.5 h was successful. The two target sequences of sialyl‐T‐glycopeptides were obtained in good yield. In contrast to the the analogs carrying the T‐antigen, the Sial‐T‐glycopeptides were non‐immunogenic, supporting the idea that the sialylation is a method of circumventing the recognition by the immune system. Copyright © 2000 John Wiley & Sons, Ltd.