Department of Basic Sciences, School of Dentistry, Ankara Yildirim Beyazit University, Ankara 06760, Turkey.
Department of Biomedical Engineering, School of Engineering and Natural Sciences Ankara Yildirim Beyazit University, Ankara 06760, Turkey.
ACS Biomater Sci Eng. 2020 Jul 13;6(7):3791-3798. doi: 10.1021/acsbiomaterials.0c00194. Epub 2020 Jun 29.
Calcium phosphate mineralizing peptides are of special importance for dental and orthopedic applications, such as caries remineralization and improved osteointegration. Uncovering the mechanism of action for such peptides is an ongoing challenge with the aim of a better fundamental understanding of biomineralization processes and developing optimized peptides for clinical use. It has recently been reported that "adjacent oppositely charged residue" motifs are found abundantly in cation binding, inorganic surface binding, or biomineralization-related proteins and may play a key role in the biomineralization events. Despite their medical importance, the role of these motifs has not yet been investigated on calcium phosphate mineral systems. To investigate this, we have designed peptides with different structural properties and different numbers of adjacent oppositely charged residues. We have evaluated their effects on calcium phosphate mineralization kinetics and mineral properties. The kinetics of the mineralization increased proportionally with an increasing number of adjacent oppositely charged residues. Two peptides with relatively high structural stability and two adjacent oppositely charged residues resulted in faster mineralization and more crystalline mineral compared to a peptide with a higher structural degree of freedom that contained only acidic residues. The fastest mineralization and the highest mineral crystallinity were obtained with a peptide containing the highest number of adjacent oppositely charged residues and highest structural degree of freedom. Our findings and observations from previously identified natural or designed peptides indicate that, in addition to structural instability, adjacent oppositely charged residues play a role in the cation binding, inorganic surface binding, and biomineralization of peptides and require further investigation. Lastly, the peptide identified in this study is an agent with potential medical applications involving the treatment of mineralized tissues.
钙磷酸盐矿化肽在牙科和骨科应用中具有特殊意义，例如龋齿再矿化和改善骨整合。揭示这些肽的作用机制是一个持续的挑战，旨在更好地理解生物矿化过程，并开发用于临床应用的优化肽。最近有报道称，“相邻的相反电荷残基”基序在阳离子结合、无机表面结合或与生物矿化相关的蛋白质中大量存在，可能在生物矿化事件中发挥关键作用。尽管这些肽具有重要的医学意义，但它们在钙磷酸盐矿化系统中的作用尚未得到研究。为了研究这一点，我们设计了具有不同结构特性和不同数量相邻相反电荷残基的肽。我们评估了它们对钙磷酸盐矿化动力学和矿物性质的影响。矿化动力学与相邻相反电荷残基数量的增加成正比增加。与仅含有酸性残基的具有较高结构自由度的肽相比，具有较高结构稳定性和两个相邻相反电荷残基的两种肽导致更快的矿化和更结晶的矿物。含有最高数量相邻相反电荷残基和最高结构自由度的肽获得最快的矿化和最高的矿物结晶度。我们的发现和以前鉴定的天然或设计肽的观察结果表明，除了结构不稳定性外，相邻的相反电荷残基在肽的阳离子结合、无机表面结合和生物矿化中也发挥作用，需要进一步研究。最后，本研究中鉴定的肽是一种具有潜在医学应用的试剂，涉及矿化组织的治疗。
