Specific Binding and Mineralization of Calcified Surfaces by Small Peptides

Abstract

Several small (<25aa) peptides have been designed based on the sequence of the dentin phosphoprotein, one of the major noncollagenous proteins thought to be involved in the mineralization of the dentin extracellular matrix during tooth development. These peptides, consisting of multiple repeats of the tripeptide aspartate-serine-serine (DSS), bind with high affinity to calcium phosphate compounds and, when immobilized, can recruit calcium phosphate to peptide-derivatized polystyrene beads or to demineralized human dentin surfaces. The affinity of binding to hydroxyapatite surfaces increases with the number of (DSS)n repeats, and though similar repeated sequences—(NTT)n, (DTT)n, (ETT)n, (NSS)n, (ESS)n, (DAA)n, (ASS)n, and (NAA)n—also showed HA binding activity, it was generally not at the same level as the natural sequence. Binding of the (DSS)n peptides to sectioned human teeth was shown to be tissue-specific, with high levels of binding to the mantle dentin, lower levels of binding to the circumpulpal dentin, and little or no binding to healthy enamel. Phosphorylation of the serines of these peptides was found to affect the avidity, but not the affinity, of binding. The potential utility of these peptides in the detection of carious lesions, the delivery of therapeutic compounds to mineralized tissues, and the modulation of remineralization is discussed.

State of the Art Enamel Remineralization Systems: The Next Frontier in Caries Management

“…8DSS peptides have essentially two mineral-binding surfaces and can strongly bind not only to free Ca 2+ and PO 4 3-ions, but also to the HA surface [George et al, 1996;Yarbrough et al, 2010]. Applying these peptides to enamel can prevent dissolution of Ca 2+ and PO 4 3-ions into the surrounding medium while promoting the capture of these ions from solution.…”

“…Several short functional peptides based on DPP have been designed as they offer a number of advantages over full-length DPP such as higher purity and better conformational fit on enamel, while avoiding allergies and immunogenicity often associated with animal proteins [Hsu et al, 2011]. Among the DPP-derived peptides, the octuplet repeats of aspartate- serine-serine (8DSS) are the most active in promoting biomineralization [Yarbrough et al, 2010].…”

Synergistic Inhibition of Enamel Demineralization by Peptide 8DSS and Fluoride

“…Such peptides bind to calcium phosphate compounds with higher affinity than do other DPP-derived peptides (e.g. DAA, ASS, NAA), and conjugating them to polystyrene beads recruits calcium phosphate to the bead surface [Yarbrough et al, 2010].…”

“…Of the various DPP-derived peptides described so far, which contain 2-8 DSS repeats, peptides containing 8 repeats (8DSS) appear to be the most active in promoting biomineralization [Yarbrough et al, 2010]. 8DSS promotes mineral deposition onto human enamel and improves the surface properties of demineralized enamel [Hsu et al, 2011a].…”

Accelerated Nucleation of Hydroxyapatite Using an Engineered Hydrophobin Fusion Protein

“…In the past, many research groups have focused on the in vitro synthesis of enamel. 1,[3][4][5][6][7][8][9][10][11][12] Protein or peptide mediated biomineralization has been found to be a promising method to reconstruct enamel because it can occur under physiological conditions to provide a biocompatible material. Detailed studies of extracellular matrix proteins during the development of enamel or dentin have led to a deeper understanding of the biomineralization process of teeth.…”