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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE006159-10
Application #
3219895
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1982-02-01
Project End
1995-01-31
Budget Start
1993-02-01
Budget End
1994-01-31
Support Year
10
Fiscal Year
1993
Total Cost
Indirect Cost
Name
New York University
Department
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
Schlesinger, D H; Hay, D I; Schluckebier, S K et al. (1994) Primary structure of a novel human salivary acidic proline-rich protein. Pept Res 7:242-7
Hay, D I; Ahern, J M; Schluckebier, S K et al. (1994) Human salivary acidic proline-rich protein polymorphisms and biosynthesis studied by high-performance liquid chromatography. J Dent Res 73:1717-26
Schlesinger, D H; Hay, D I; Levine, M J (1989) Complete primary structure of statherin, a potent inhibitor of calcium phosphate precipitation, from the saliva of the monkey, Macaca arctoides. Int J Pept Protein Res 34:374-80
Audhya, T; Hollander, C S; Schlesinger, D H et al. (1989) Structural characterization and localization of corticotropin-releasing factor in testis. Biochim Biophys Acta 995:10-6
Hay, D I; Bennick, A; Schlesinger, D H et al. (1988) The primary structures of six human salivary acidic proline-rich proteins (PRP-1, PRP-2, PRP-3, PRP-4, PIF-s and PIF-f). Biochem J 255:15-21
Schlesinger, D H; Buku, A; Wyssbrod, H R et al. (1987) Chemical synthesis of phosphoseryl-phosphoserine, a partial analogue of human salivary statherin, a protein inhibitor of calcium phosphate precipitation in human saliva. Int J Pept Protein Res 30:257-62
Hay, D I; Carlson, E R; Schluckebier, S K et al. (1987) Inhibition of calcium phosphate precipitation by human salivary acidic proline-rich proteins: structure-activity relationships. Calcif Tissue Int 40:126-32
Nakane, T; Audhya, T; Hollander, C S et al. (1986) Corticotrophin-releasing factor in extra-hypothalamic brain of the mouse: demonstration by immunoassay and immunoneutralization of bioassayable activity. J Endocrinol 111:143-9
Schlesinger, D H; Hay, D I (1986) Complete covalent structure of a proline-rich phosphoprotein, PRP-2, an inhibitor of calcium phosphate crystal growth from human parotid saliva. Int J Pept Protein Res 27:373-9
Vergara, U; Gwadz, R; Schlesinger, D et al. (1985) Multiple non-repeated epitopes on the circumsporozoite protein of Plasmodium knowlesi. Mol Biochem Parasitol 14:283-92