Effects of glycosylation on fragments of tumour 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 glycopeptides and the control, non-glycosylated decapeptide AcPAPGSTAPPA have been investigated using NMR spectroscopy. The structural studies indicate that the glycohexapeptide has a folded structure in solution. For this molecule, unrestrained molecular dynamics has been used to confirm the presence of the observed solution through-space connections. The results indicate that the non-globular nature of MUC1 is due to both protein core sequence and the effect of carbohydrate.
Braun
P
P
Institut für Organische Chemie, Universität Mainz, Germany.
Davies
G M
GM
Price
M R
MR
Williams
P M
PM
Tendler
S J
SJ
Kunz
H
H
D000595:Amino Acid Sequence; D006031:Glycosylation; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011487:Protein Conformation; D016339:Spectrometry, Mass, Fast Atom Bombardment
D018396:Mucin-1; D010446:Peptide Fragments