Nucleation and growth inhibition of biological minerals by cementum attachment protein‐derived peptide (CAP‐pi)

Abstract

Biomineralization is a highly regulated process where proteins/peptides-crystal interactions contribute to the shaping, phasing and aggregation of minerals. We have identified and synthesized a cementum attachment protein-derived peptide (CAP-pi), which corresponds to amino acids 40-53 of the N-terminal CAP domain (MASSDEDGTNGGAS) and its phosphorylated variant (MASpSpDEDGTNGGASp) (CAP-pip). The peptide is composed of polar and negatively charged amino acids, which are disordered, according to in silico analysis. Our results show that CAP-pi inhibits hydroxyapatite (HA) formation and growth. However, it possesses low capacity to inhibit calcium oxalate crystal growth. CAP-pip showed a stronger inhibitory effect on the formation and growth of HA. As well as a high capacity to inhibit calcium oxalate monohydrate growth, mainly due to adsorption on specific growth faces. Small peptides have many advantages over the full-size protein, including lowcost production and modulation characteristics that allow for structural changes. Our findings suggest that CAP-pip-derived peptide could possess therapeutic potential to prevent or treat pathological calcifications such as renal stones and vascular calcification.

Influence of Divalent Metal Ions on the Precipitation of the Plasma Protein Fibrinogen

“…This observation indicates a clear contribution of fibrinogen to the drying of the respective salts, which can be interpreted as a "smoothing contribution" of the protein on salt precipitation. 59,61 Furthermore, in general, fibrinogen seems to delay salt precipitation. Interestingly, when fibrinogen was dried in Tris alone, the Aq roughness was close to zero throughout the whole drying process, and the same trend was observed when Tris was dried without any fibrinogen (see Figure 2E).…”

Bioactive Synthetic Peptides for Oral Tissues Regeneration

“…Peptides Derived from the Amino Acid Sequence of Cementum Proteins Some SP derived from dental cementum proteins such as CEMP-1 (CEMP-1-p1) and HACD1/CAP (CAP-pi) have biological activity associated with the in vitro biomineralization (Correa et al, 2019;Montoya et al, 2019;Montoya et al, 2020). CEMP-1-p1 induces the formation of spherical mineral structures on a nanometric scale and with a well-defined growth center of OCP (Correa et al, 2019).…”

“…CEMP-1-p1 induces the formation of spherical mineral structures on a nanometric scale and with a well-defined growth center of OCP (Correa et al, 2019). CAP-pi shows inhibitory activity of mineral crystal nucleation and growth (Montoya et al, 2020). The behavior of CEMP1-derived peptides is related to their capacity to activate Wnt/β-catenin signaling pathways, which is associated with the enhancement of the biomineralization process (Arroyo et al, 2020).…”

Amorphous titanium oxide (aTiO2) thin films biofunctionalized with CAP-p15 induce mineralized-like differentiation of human oral mucosal stem cells (hOMSCs)

“…This sequence of 15 amino acid residues is derived from the C-terminal region of the cementum attachment protein (CAP) and possesses acidic and hydrophobic properties. More importantly, CAP-p15 exhibited the ability to facilitate carbonate hydroxyapatite crystal formation, enhancing cell attachment, influencing cytoskeleton organization, and improving cell proliferation and migration of human periodontal ligament cells in vitro [16][17][18].…”