Structural and computational investigations of the conformation of antigenic peptide fragments of human polymorphic epithelial mucin.

摘要: Human polymorphic epithelial mucins (PEM) are complex glycoproteins that associated with breast and ovarian carcinomas. The PEM core protein consists of variable numbers a tandem repeat sequence which contains short antigenic hydrophilic region (Pro1-Asp-Thr-Arg-Pro-Ala-Pro7). High-field n.m.r. studies undertaken on 20- 11-amino acid fragments the in dimethyl sulphoxide have identified type-I beta-turn to be present Pro1-Asp-Thr-Arg4. This includes overlaps (Asp2-Thr-Arg4) type-II (Arg4-Pro-Ala6) epitopes anti-PEM monoclonal antibodies. indicate is stabilized by presence salt-bridge interaction between Asp-2 Arg-4. In order probe conformations accessible peptides computational study was independently peptide Pro-Asp-Thr-Arg-Pro using modified Metropolis Monte Carlo algorithm. n.m.r.-observed as major low-energy conformer. These results suggest this structural motif may involved immune recognition PEM.