The acidic anionic proline-rich proteins, a major component in and important class of protein inhibitors of calcium phosphate precipitation in human salivary secretions, are also potent modulators of bacterial adhesion onto the tooth and hydroxyapatite surfaces. A comparison of adhesion-promoting activity of the major gene products, the 150 amino acid protein and its major cleavage product (residues 1-106) and of the three tryptic peptides comprising the 150 residue native protein indicates that the adhesive properties of the molecule reside in the C-terminal 44 amino acid domain. Peptide synthesis of di- through deca-peptides comprising the C-terminus indicated that this activity is further localized in the C-terminal tetrapeptide. Additional peptide syntheses of glycine-substituted decapeptides further refines this domain to the C-terminal dipeptide. Stereochemical modifications of residues 149 and 150 demonstrate the essentiality of a ring structure in the penultimate residue and a precise aliphatic side chain length as well as a free-alpha carboxyl group in the C-terminal position. Substitution of thioproline for proline in the penultimate position results in a glycine-substituted (positions 141-148) analog more active than the native intact PRPs. Such studies provide the possibility of synthetic peptide analogs of the PRPs as inhibitors of the bacterial adhesive process which leads to the formation of dental plaque and to the early phases of periodontal disease and dental caries.
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