Human salivary MUC7 mucin fragment and its analogues. Coordination and biological studies

Mucin 7 (called MUC7 or MG2) is a salivary protein whose fragments exhibit a strong antimicrobial activity and is a natural protection of organisms against pathogens. Up to date however the exact mechanism of their actions is unknown. One hypothesis covers an involvement of biologically occurring metal ions in this process. Herein, three 12-mer peptides have been included in the study, one of which (mother-peptide sequence, L3) is a direct analogue of a fragment naturally cut out from the MUC7 (with His3 and His8) and its two structural analogues, containing only one histidine residues His3 or His8 (L2 and L1, respectively), which are essential for binding to metal ions. Antimicrobial properties of the studied peptides as well as their complexes have been tested against bacterial and fungal strains revealing activity towards Gramm-positive bacteria (Enterococcus faecalis and Staphylococcus epidermidis) which were slightly enhanced upon Cu(II) or Zn(II) ions coordination. The study of both the biological and thermodynamic properties of considered systems has not been measured before. Exact coordination studies (potentiometry, ultraviolet/visible spectroscopy - UV-Vis, circular dichroism spectroscopy - CD) revealed the formation of mainly mono-nuclear complexes in solution for all studied systems in which the binding abilities turned out to be inversely proportional to the antimicrobial properties exhibited. However, distinctly different lipophilicity of peptides, the reduction of which (also upon metal coordination) increases the ability to inhibit the growth of E. faecalis and S. epidermidis strains, seems to be the most important factor of their activity.