Konformationsanalytische Untersuchungen von N-terminalen O-Glycopeptidsequenzen des Interleukin-2

The preferred conformations of eight O -glycopeptide sequences from the N -terminus of interleukin-2 containing two to ten amino acids, monoglycosylated at Thr 3 with a 2-acetamido-2-deoxy-α- d - galactopyranosyl group, were determined by means of n.m.r. spectroscopic methods. The preferred conformation of the N-terminal sequence, l -Ala- l -Pro-[α- d -Gal p NAc-(1→3)]- l -Thr- l -Ser, including the O -glycosidically linked 2-acetamido-deoxy-α- d -galactopyranosyl group is not substantially influenced by the linkage of additioinal amino acids at the C-terminal end. Extended conformations were observed for all peptide units. Measurements of the relaxation times of the 13 C atoms showed that the 2-acetamido-2-deoxy- d -galactose bound to the central amino acids has the lowest mobility, whereas the terminal amino acid residues and peptide side-chains are flexible. Calculations with the force-field program AMBER yielded conformations of minimized energies that were in good agreement with the n.m.r. spectroscopic data. This was only true when n.m.r. parameters that can be used as starting values for the calculations were available. Comparison with a nonglycosylated, N-terminal tetrapeptide sequence analog did not suggest changes in the peptide conformation when Thr 3 is glycosylated with a 2-acetamido-2-deoxy-α- d -galactopyranosyl group.