EFFECTS OF GLYCOSYLATION ON FRAGMENTS OF TUMOR-ASSOCIATED HUMAN EPITHELIAL MUCIN MUC1

The glycodecapeptide AcPAPGS(alpha GalNAc)T(alpha GalNAc)APPA and the C-terminal glycohexapeptide AcS(alpha GalNAc)T(alpha GalNAc)APPA have been synthesized by applying the N-terminal Fmoc group in combination with the heptyl ester cleavable by lipase-catalyzed hydrolysis at pH 7 . The solution conformation of these MUC1-related synthetic glycopepti des and the control, non-glycosylated decapeptide AcPAPGSTAPPA have be en investigated using NMR spectroscopy. The structural studies indicat e that the glycohexapeptide has a folded structure in solution. For th is molecule, unrestrained molecular dynamics has been used to confirm the presence of the observed solution through-space connections. The r esults indicate that the non-globular nature of MUC1 is due to both pr otein core sequence and the effect of carbohydrate. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.