Nabeela Abbasi, Jelena Kosoric, Nauman Bari, Beenish Fatima Alam, Syed Jaffar Abbas Zaidi, Paul Anderson.
Influence of N-terminals statherin pentapeptide sequence residues on cariostatic efficacy.
Pak Oral Dental J Jan ;40(1):40-6.

In vitro studies have shown that Statherin (StN43) and its shortened analogues containing only the N-terminal 21 amino acids (StN21) inhibit demineralization under artificial cariogenic challenges. This has been shown by experimentally and computationally to be associated with interactions of specific N-terminal residues with hydroxyapatite surfaces. The aim of this study was to identify which of the first 5 N-terminal residues are most important for reducing the rate of demineralization under artificial caries conditions, using scanning microradiography (SMR). Five statherin21-like peptides were prepared using FMOC synthesis with each of the N-terminal five residues of StN21 replaced by the non-polar residue alanine and dissolved in phosphate buffer at pH 7.4 (0.188 mM). HA pellets (20% porosity) used as model substrates for enamel demineralization studies were sectioned and mounted in scanning microradiography (SMR) environmental cells and exposed to 0.1M acetic acid at pH4.0 for 72h. The sections were then treated with one of the StN21 solutions for 24h, then demineralization continued for a further 72h. SMR was used to measure demineralization rates (RDHA) before and after peptide treatment. Treating with StN21 resulted in 43% reduction in RDHA. StN21 peptides in which the phosphorylated serine at position 2 was replaced only reduced RDHA by 32%. For StN21 peptide with the phosphorylated serine at position 3 replaced, RDHA was not reduced. Replacement at position 5 (glutamate) also reduced RDHA by only 32%. Replacements at residue positions 1 and 4 showed the maximum reduction in RDHA by 52% and 50% respectively. In conclusion, the phosphorylated serine residue at N-terminal position 3 of Statherin is required to inhibit demineralization. Other important residues, but to a lesser extent, are the phosphorylated serine at position 2, and the glutamic acid at position 5. These studies demonstrate that the molecular architecture arrangements of Statherin are required for cariostatic efficacy.

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