Unraveling mechanism for an amelogenin-derived peptide regulated hydroxyapatite mineralization via specific functional domain identification
Amelogenin and its various derived peptides played important roles in promoting biomimetic mineralization of enamel. Previously, an amelogenin-derived peptide named QP5 was proved to be able to repair demineralized enamel. The objective here was to interpret the mechanism of QP5 through elucidating specific function of each domain for the further sequence and efficacy improvement. Peptide QP5 was separated into domains of (QPX)5 and C-tail. (QPX)3 was also synthesized to investigate how QPX repeats affect mineralization process. Circular dichroism spectroscopy showed two (QPX) reapts adopted β-sheets while C-tail exhibited a disordered structure. (QPX)5 showed more absorption in confocal laser scanning microscopy observation and higher K value in Langmiur adsorption isotherms than C-tail, while (QPX)3 with better hydropathy had a greater adsorption capability than (QPX)5. Meanwhile, calcium consumption kinetics, transmission electron microscopy and selected area electron diffraction indicated that (QPX)5, C-tail and (QPX)3 had similar inhibitory effects on the spontaneous calcium consumption and the morphology of their nucleation products were alike, while QP5 had greater inhibitory effect than them and induced elongated plate-like crystals. X-ray diffraction further showed both C-tail and (QPX)3 owned larger potential to improve apatite crystal orientation degree. In conclusion, (QPX)5 was the major adsorption region, both (QPX)5 and C-tail inhibited the nucleation, and C-tail contributed more to improve the HAP orientation degree, so QP5 could exert a significant remineralization effect. By reducing two repeats, (QPX)3 showed higher hydropathicity than (QPX)5, and achieved higher binding affinity, more potential in improving HAP orientation degree, and lower economic cost.