Synthetic Tumor-Associated Glycopeptide Antigens from the Tandem Repeat Sequence of the Epithelial Mucin MUC4

Constanze Brocke; Horst Kunz

doi:10.1055/s-2004-815962

PAPER

Synthetic Tumor-Associated Glycopeptide Antigens from the Tandem Repeat Sequence of the Epithelial Mucin MUC4

Constanze Brocke, Horst Kunz*
Institut für Organische Chemie, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128 Mainz, Germany
Fax: +49(6131)3924786; e-Mail: hokunz@mail.uni-mainz.de;

Abstract

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Abstract

In cancer research, the development of vaccines against tumor-associated antigens is of particular interest. Epithelial cells express mucin type glycoproteins, which are extensively O-glycosylated. In case of cancer, the expression of these mucins is increased, and their carbohydrate side chains show an aberrant glycosylation pattern. A set of single and double glycosylated hexadecapeptides representing the tandem repeat sequence of the epithelial mucin MUC4 carrying different tumor-associated carbohydrate antigens was prepared by sequential solid-phase glycopeptide synthesis. The crucial glycosyl amino acid building blocks containing the T_N, T, sialyl-T_N and (2,6)-sialyl-T antigens were synthesized according to a biomimetic strategy by stepwise extension of the saccharide side chain of a Fmoc-protected galactosamine threonine tert-butyl ester precursor.

Key words

glycopeptides - glycosylations - mucin MUC4 - sialyl-T antigen - solid-phase synthesis

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