Design and synthesis of polytripeptide (leuglnpro)n based upon the matrix protein amelogenin

Sogah, Dotsevi Y.; Perle-Treves, Daniele; Voyer, Normand; DeGrado, William

doi:10.1002/masy.19940880112

Cited by 7 publications

(25 citation statements)

References 17 publications

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“…Interestingly, the addition of monovalent metal ions did not affect the structural organization of the peptide. XRD studies of the amelogenin mimic peptide support the notion that the midsection of amelogenin adopts an extended conformation with a 16 5 helix secondary structure and exists as isolated "rigid rods" (Sogah et al, 1994).…”

Section: Spectroscopymentioning

confidence: 75%

“…Based on the spectroscopic data, the author proposed that the peptide adopts a ␤-spiral structure. In another CD study, (Leu-Gln-Pro) n peptides, also mimicking the center section of bovine amelogenin, were investigated (Sogah et al, 1994). When solubilized in TFE, the peptide existed primarily in an extended unordered state; however, the addition of multivalent metal ions (e.g., Ca 2+ , Mg 2+ , Sr 2+ , and Ba 2+ ) significantly increased the organization of the polypeptide, leading to the formation of repeating class C type I ␤-turn structures.…”

Section: Spectroscopymentioning

confidence: 99%

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Role of Macromolecular Assembly of Enamel Matrix Proteins in Enamel Formation

2006

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Unlike other mineralized tissues, mature dental enamel is primarily (> 95% by weight) composed of apatitic crystals and has a unique hierarchical structure. Due to its high mineral content and organized structure, enamel has exceptional functional properties and is the hardest substance in the human body. Enamel formation (amelogenesis) is the result of highly orchestrated extracellular processes that regulate the nucleation, growth, and organization of forming mineral crystals. However, major aspects of the mechanism of enamel formation are not well-understood, although substantial evidence suggests that protein-protein and protein-mineral interactions play crucial roles in this process. The purpose of this review is a critical evaluation of the present state of knowledge regarding the potential role of the assembly of enamel matrix proteins in the regulation of crystal growth and the structural organization of the resulting enamel tissue. This review primarily focuses on the structure and function of amelogenin, the predominant enamel matrix protein. This review also provides a brief description of novel in vitro approaches that have used synthetic macromolecules (i.e., surfactants and polymers) to regulate the formation of hierarchical inorganic (composite) structures in a fashion analogous to that believed to take place in biological systems, such as enamel. Accordingly, this review illustrates the potential for developing bio-inspired approaches to mineralized tissue repair and regeneration. In conclusion, the authors present a hypothesis, based on the evidence presented, that the full-length amelogenin uniquely regulates proper enamel formation through a process of cooperative mineralization, and not as a pre-formed matrix.

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Section: Spectroscopymentioning

confidence: 75%

Section: Spectroscopymentioning

confidence: 99%

Role of Macromolecular Assembly of Enamel Matrix Proteins in Enamel Formation

2006

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“…Higher molar ratios of NaCl were necessary to produce similar changes in the 1 H– 15 N spectra observed with CaCl 2 , and this is likely related, at least partially, to the three-times greater ionic strength of CaCl 2 over NaCl (at equal concentrations). Multivalent metal ions have been observed to influence the secondary structure of the HQP-rich region of amelogenin (36), and hence, some of the differences in the details between the NaCl and CaCl 2 titrations may be ion related (Na + versus Ca 2+ ) (5) and serve a functional purpose. It is interesting to note that with both NaCl and CaCl 2 , relatively high ionic strengths in the NMR tube (300 and 495 mM, respectively, at the final titration point) were required to observe the spectral changes in both the N- and C-termini, and this is consistent with the high ionic strength of 165 mM measured in the enamel fluid from developing pig teeth (37).…”

Section: Resultsmentioning

confidence: 99%

A Solution NMR Investigation into the Early Events of Amelogenin Nanosphere Self-Assembly Initiated with Sodium Chloride or Calcium Chloride

et al. 2008

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Using solution-state NMR spectroscopy, new insights into the early events governing amelogenin supramolecular self-assembly have been identified using sodium chloride and calcium chloride to trigger the association. Two-dimensional 1 H-15 N HSQC spectra were recorded for 15 N-and 13 Clabeled murine amelogenin as a function of increasing NaCl and CaCl 2 concentration beginning with solution conditions of 2% acetic acid at pH 3.0, where amelogenin was monomeric. Residue specific changes in molecular dynamics, manifested by the reduction in intensity and disappearance of 1 H-15 N HSQC cross-peaks, were observed with the addition of either salt to the protein. With increasing NaCl concentrations, residues between T21 and R31 near the N-terminus were affected first, suggesting that these residues may initiate amelogenin dimerization, the first step in nanosphere assembly. At higher NaCl concentrations, more residues near the N-terminus (Y12-I51) were affected, and with further additions of NaCl, residues near the C-terminus (L141-T171) began to show a similar change in molecular dynamics. With increasing CaCl 2 concentrations, a similar stepwise change in molecular dynamics involving essentially the same set of amelogenin residues was observed. As the concentration of either salt was increased, a concomitant increase in the estimated overall rotational correlation time (τ c ) was observed, consistent with assembly. Selfassembly into a dimer or trimer was established with dynamic light scattering studies under similar conditions that showed an increase in diameter of the smallest species from 4.1 nm in the absence of salt to ~10 nm in the presence of salt. These results suggest a possible stepwise interaction mechanism, starting with the N-terminus and followed by the C-terminus, leading to amelogenin nanosphere assembly.Dental enamel, the layer of elongated carbonated hydroxayapatite on the outer layer of the tooth, is the hardest tissue in the human body (1). It needs to be strong because it is exposed to repeated masticatory, parafunctional, and occasional impact loading, but unlike the dominant biomineral in the human body (2), mesenchyme-derived bone, enamel cannot self-repair nor can it undergo remodeling, and therefore, it must last a lifetime. Enamel's resistance to wear and deformation are due to a combination of high mineral content and unique three-dimensional structural organization (3). Ninety-five percent of mature enamel consists of long and narrow crystals of carbonated hydroxyapatite packed into parallel arrays, called enamel rods, that are intricately interwoven into an unique lattice architecture (4,5). There is little, if any, matrix

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“…Peaks observed at 1,620–1,630 cm −1 were identified as hydrated PPII helix (Johnston and Krimm, 1971 ; Wellner et al, 1996 ; Elangovan et al, 2007 ). Earlier reports indicate that the full length amelogenins contain a significant PPII fraction (Renugopalakrishnan et al, 1986 ; Goto et al, 1993 ; Sogah et al, 1994 ; Lakshminarayanan et al, 2007 , 2009 ). In an overlapped region to this, peaks observed between 1,610 and 1,640 cm −1 were attributed to β-sheet (Susi and Byler, 1983 ; Jackson and Mantsch, 1995 ).…”

Section: Methodsmentioning

confidence: 97%

Protein Phosphorylation and Mineral Binding Affect the Secondary Structure of the Leucine-Rich Amelogenin Peptide

et al. 2017

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Previously, we have shown that serine-16 phosphorylation in native full-length porcine amelogenin (P173) and the Leucine-Rich Amelogenin Peptide (LRAP(+P)), an alternative amelogenin splice product, affects protein assembly and mineralization in vitro. Notably, P173 and LRAP(+P) stabilize amorphous calcium phosphate (ACP) and inhibit hydroxyapatite (HA) formation, while non-phosphorylated counterparts (rP172, LRAP(−P)) guide the growth of ordered bundles of HA crystals. Based on these findings, we hypothesize that the phosphorylation of full-length amelogenin and LRAP induces conformational changes that critically affect its capacity to interact with forming calcium phosphate mineral phases. To test this hypothesis, we have utilized Fourier transform infrared spectroscopy (FTIR) to determine the secondary structure of LRAP(−P) and LRAP(+P) in the absence/presence of calcium and selected mineral phases relevant to amelogenesis; i.e., hydroxyapatite (HA: an enamel crystal prototype) and (ACP: an enamel crystal precursor phase). Aqueous solutions of LRAP(−P) or LRAP(+P) were prepared with or without 7.5 mM of CaCl2 at pH 7.4. FTIR spectra of each solution were obtained using attenuated total reflectance, and amide-I peaks were analyzed to provide secondary structure information. Secondary structures of LRAP(+P) and LRAP(−P) were similarly assessed following incubation with suspensions of HA and pyrophosphate-stabilized ACP. Amide I spectra of LRAP(−P) and LRAP(+P) were found to be distinct from each other in all cases. Spectra analyses showed that LRAP(−P) is comprised mostly of random coil and β-sheet, while LRAP(+P) exhibits more β-sheet and α-helix with little random coil. With added Ca, the random coil content increased in LRAP(−P), while LRAP(+P) exhibited a decrease in α-helix components. Incubation of LRAP(−P) with HA or ACP resulted in comparable increases in β-sheet structure. Notably, however, LRAP(+P) secondary structure was more affected by ACP, primarily showing an increase in β-sheet structure, compared to that observed with added HA. These collective findings indicate that phosphorylation induces unique secondary structural changes that may enhance the functional capacity of native phosphorylated amelogenins like LRAP to stabilize an ACP precursor phase during early stages of enamel mineral formation.

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Design and synthesis of polytripeptide (leuglnpro)n based upon the matrix protein amelogenin

Cited by 7 publications

References 17 publications

Role of Macromolecular Assembly of Enamel Matrix Proteins in Enamel Formation

Role of Macromolecular Assembly of Enamel Matrix Proteins in Enamel Formation

A Solution NMR Investigation into the Early Events of Amelogenin Nanosphere Self-Assembly Initiated with Sodium Chloride or Calcium Chloride

Protein Phosphorylation and Mineral Binding Affect the Secondary Structure of the Leucine-Rich Amelogenin Peptide

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