Human saliva is highly supersaturated with respect to basic calcium phosphate salts. However, precipitation of these salts from saliva and crystal growth of calcium phosphates onto dental enamel do not occur under normal physiological conditions. This unexpected stability is due to the inhibitory activities of two kinds of salivary phosphoproteins, statherin and the acidic proline-rich phosphoproteins (PRP). At physiological conditions, staterin inhibits spontaneous precipitation and crystal growth of calcium phosphates, whereas the PRP act as potent inhibitors of crystal growth by adsorbing onto surfaces of calcium phosphate minerals, such as dental enamel mineral. These activities are of biological significance in that they act to provide a supersaturated, but stable, protective and reparative environment for the dental enamel, which is important for the integrity of the teeth. The basic objective of this project is to relate the primary structure of these inhibitors to their functions in the oral cavity. The most rigorous way of attacking this problem is via chemical synthesis of analogs of these novel phosphoproteins and to study their activities of these analogs in inhibiting primary and secondary precipitation of calcium phosphate salts. Recently, we developed a novel and efficient strategy for preparing any desired synthetic phosphoserine-containing analog of staterin and the PRPs and a wide variety of such analogs are planned. Recently, it has been shown that the PRPs and statherin, when adsorbed onto apatitic minerals, can act to promote adhesion of several prominent oral bacteria. Consequently, we are also planning the chemical synthesis of analogs of the C-terminus of statherin and the PRPs to investigate these adhesive reactions on a molecular level. We are continuing to study the evolution of these inhibitors and are presently determining their structures in the saliva of the red kangaroo and other mammalian species.
