Accelerated Calcium Phosphate Mineralization by Peptides with Adjacent Oppositely Charged Residues

Abstract

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 in vitro 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.

Understanding the Adhesion Mechanism of Hydroxyapatite-Binding Peptide

“…These seemingly contradicting results emphasize the complexity of these systems. Moreover, it was previously shown that conformation has a role in the interaction with solid surfaces. − …”

In vitro remineralization of primary teeth with a mineralization-promoting peptide containing dental varnish

“…The peptide used in this study is proposed to act by attracting the available calcium and phosphate ions, thus, creating local supersaturation zones. 24 In contrast, existing products provide the fluoride (and calcium and phosphate) to a relatively larger area within the lesion, which may explain the higher number of subsurface lesions observed.…”

“…Preparation of the varnishes: The peptide used in this study (PGEKADRAEKADRA) 24 was synthesized commercially at >98% purity (GenScript Biotech Corp. NJ, USA). Natural colophony was used to prepare the peptide-containing varnishes.…”

“…The peptide concentration was based on previous studies using similar peptides. 15 , 24 Peptide and NaF were dissolved in ethanol and added to the colophony. A placebo varnish was prepared with blank colophony, containing no peptide or NaF.…”

Periodontal Tedavilerde Amelogenin (Emdogain) ve Mineralizan Peptid Uygulamaları

“…21 Daha güncel bir çalışmada, amelogeninde ve mineralizasyonda rol alan diğer çoğu proteinde gözlemlenen bitişik zıt yüklü amino asitlerin varlığından yola çıkılarak tasarlanan 14 amino asitlik daha kısa ve mineral oluşum kinetiğini ADP5'e göre daha fazla artıran bir peptit elde edilmiştir. 22 Mineral promoting peptide-3 (MPP3) adı verilen bu peptit bir vernik içerisinde yapay mine lezyonlarına uygulandığında lezyon derinliğinde sadece flor içeren verniklere eşdeğer bir azalma sağlamıştır. Florla kombine edilerek kullanıldığında ise lezyon derinliğinde sadece flor içeren verniklere göre daha fazla azalma sağlamıştır.Yine adheziv uygulaması öncesinde dentin yüzeyi MPP3 ile muamele edildiğinde adhezyonu artıran ve mikrosızıntıyı azaltan bir mineral tabakası oluşturduğu gösterilmiştir.…”