A Polyproline II Motif is Determined in MUC1 Mucin Synthetic (Glyco)-Peptides Using CD And NMR

Abstract

MUC1 mucin is a heavily glycosylated glycoprotein found on the apical side of normal human epithelial cells but is aberrantly glycosylated and over-expressed on cancerous epithelial cells. It contains multiple repeats of the 20 amino acid sequence TAPPAHGVTSAPDTRPAPGS which contains the immunodominant sequence APDTRPAPG in which all anti-MUC1 monoclonal antibodies are known to bind. This study looks at the effects of N-acetyl galactosamine (GalNAc) sugar glycosylation of the peptide repeat sequence on its secondary conformation using circular dichroism (CD) and nuclear magnetic resonance (NMR). This glycosylation has been shown to affect antibody binding to the MUC1 peptide core (Spencer et al., 1996, Denton et al., in press).