Identification of Key Functional Motifs of Native Amelogenin Protein for Dental Enamel Remineralisation

Abstract

Dental caries or tooth decay is a preventable and multifactorial disease that affects billions of people globally and is a particular concern in younger populations. This decay arises from acid demineralisation of tooth enamel resulting in mineral loss from the subsurface. The remineralisation of early enamel carious lesions could prevent the cavitation of teeth. The enamel protein amelogenin constitutes 90% of the total enamel matrix protein in teeth and plays a key role in the biomineralisation of tooth enamel. The physiological importance of amelogenin has led to the investigation of the possible development of amelogenin-derived biomimetics against dental caries. We herein review the literature on amelogenin, its primary and secondary structure, comparison to related species, and its’ in vivo processing to bioactive peptide fragments. The key structural motifs of amelogenin that enable enamel remineralisation are discussed. The presence of several motifs in the amelogenin structure (such as polyproline, N- and C-terminal domains and C-terminal orientation) were shown to play a critical role in the formation of particle shape during remineralization. Understanding the function/structure relationships of amelogenin can aid in the rational design of synthetic polypeptides for biomineralisation, halting enamel loss and leading to improved therapies for tooth decay.

Bioactive Synthetic Peptides for Oral Tissues Regeneration

“…Also, more than 40 trace elements have been identified in enamel, which can be incorporated in various ways: ion exchange in the hydration shell, which is the layer of water adjacent to the crystal; direct absorption on the surface of the crystal; and substitution with components of the crystal of similar size and charge. The acid solubility of a tooth and thus its caries resistance can be affected by the crystal size and shape, and the proximity of the crystals (Hara and Zero, 2010;Kind et al, 2017;González-Cabezas and Fernández, 2018;Dissanayake et al, 2020;Farooq and Bugshan, 2020).…”

“…Besides, DPSCs increases early vascular network formation and increases VEGF expression grown enamel-like layer exhibits well-regulated crystal growth and improved composition, structure, and mechanical properties of artificial enamel (Yarbrough et al, 2010;Buzalaf et al, 2017;Prajapati et al, 2018;Bröseler et al, 2020;Farooq and Bugshan, 2020). The tyrosine-rich peptides (TRAP) domain derived from amelogenin N-terminus has been associated with matrix selfassembly meanwhile, the amelogenin central polyproline repeat region could control crystal spacing, and the hydrophilic C-terminus facilitates amelogenin protein solubility and its adhesion to the crystal surface (Han et al, 2017;Dissanayake et al, 2020;Farooq and Bugshan, 2020;Wang et al, 2020). On the other hand, leucine-rich peptides (LRAP) can promote both, enamel crystal nucleation and growth in mouse models (Ding et al, 2020).…”

“…On the other hand, leucine-rich peptides (LRAP) can promote both, enamel crystal nucleation and growth in mouse models (Ding et al, 2020). LRAP improves the remineralization of enamel surface lesions on extracted teeth in vitro more effectively than full-length amelogenin (Han et al, 2017;Dissanayake et al, 2020;Farooq and Bugshan, 2020;Wang et al, 2020) and has been modified with phosphorylation using a calcium and phosphaterich solution forming spherical nanoparticles in a linear chainlike pattern. These self-assembled peptides formed spherical amorphous calcium phosphate (ACP) particles and triggered ACP to hydroxyapatite phase transformation (Ieong et al, 2011;Bagheri et al, 2015;González-Cabezas and Fernández, 2018;Arifa et al, 2019;Mukherjee et al, 2019;Pandya and Diekwisch, 2019;Dissanayake et al, 2020;Farooq and Bugshan, 2020).…”

“…Regarding self-assembled peptides, these can form a threedimensional scaffold and can promote early caries/white lesion remineralization (Pandya and Diekwisch, 2019;Bröseler et al, 2020;Dissanayake et al, 2020;Farooq and Bugshan, 2020;Li et al, 2020). For instance, P11-4 is an N-terminally acetylated, C-terminal amidated, 11 amino acid residue peptide.…”

“…In the case of the fourth-generation polyamidoamine dendrimer (PAMAM-Po3H2) which mimic the self-assembly behavior of amelogenins, it is used as an organic template to induce crystal remineralization with the same structure, orientation, and mineral phase of the intact enamel in a relatively short time (Brunton et al, 2013;Kind et al, 2017;Alkilzy et al, 2018b;Arifa et al, 2019;Pandya and Diekwisch, 2019;Üstün and Aktören, 2019;Bröseler et al, 2020;Dissanayake et al, 2020;Farooq and Bugshan, 2020;Wang et al, 2020). Another strategy is to form films by amyloid-like lysozyme to obtain β-sheet stacked, which are combined with synthetic peptide based on the functional domains of C-terminal of amelogenin to promotes the oriented growth of HA crystals, which have a hardness and interfacial bonding stability higher than those of enamel repaired by fluoride.…”