SPICULE MATRIX MOTIFS--MODEL FOR DENTAL MATERIALS

在牙科医学中，需要新型生物材料，用于 骨和牙齿重建和颅面再生 和牙周组织。 我们的研究旨在了解 天然生物聚合物与生物矿物相互作用形成复合材料。 我们的模型系统是海胆骨针，一种矿物基质复合物 由方解石（CaCO 3）和45种基质蛋白组成的物质。 最近的研究表明，骨针基质蛋白显然 成为“截留”或嵌入在方解石超晶格中， 生物矿化过程由于这种插入， 钙化骨针表现出增加的抗断裂性， 人造方解石当断裂发生时，“玻璃状”断裂特性 被观察到。 这些材料特性非常适合 牙科材料应用。 我们提出了一个初步的多学科 插入蛋白SM 50研究我们的目标是确定 -Gln-Pro-Gly-（QPG）和-Pro-Asn-Asn-的三维结构 Pro-（PNNP）序列重复包含在该蛋白质内。 主 本研究的工具是（A）NMR光谱学和（B）分子 建模与仿真。在（A）中，我们将合成以下肽模拟物： QPG和PNNP基序，并进行NMR实验，以确定 解这些序列重复的构象状态。 在（B）中，我们 将使用计算算法来确定低能量状态， 来源于SM 50基序序列的多肽。使用结构 从每种肽中获得的信息，我们可以推断这些数据， SM 50的重复区域，占蛋白质的近50%， 顺序使用这个“积累”模型，我们可以开始探索 SM 50结构可能“包装”在一个方解石超晶格，或者， 蛋白质的区域可用于蛋白质-蛋白质缔合。 这些方法应该为我们提供有关 SM 50嵌入蛋白的结构，并最终将铺平道路， 合成聚合物的合理设计的方式，将执行 嵌入蛋白在牙科材料中的作用。

In dental medicine, there is a need for novel biomaterials for use in osseous and tooth reconstruction and in the regeneration of craniofacial and periodontal tissues. Our research is directed at understanding how natural biopolymers interact with biominerals to form composite materials. Our model system is the sea urchin spicule, a mineral matrix composite material that is comprised of calcite (CaCO3) and 45 matrix proteins. Recent developments indicate that the spicule matrix proteins apparently become "entrapped" or intercalated within the calcite superlattice during the biomineralization process. As a result of this intercalation, the calcitic spicule exhibits increased resistance to fracture, compared to synthetic calcite. When fracture does occur, "glassy" fracture properties are observed. These material properties would be ideally suited for dental materials applications. We propose an initial multidisciplinary investigation of SM50, an intercalation protein. Our goal is to determine the three-dimensional structure of -Gln-Pro-Gly- (QPG) and -Pro -Asn-Asn- Pro- (PNNP) sequence repeats contained within this protein. The primary tools for this study will be (A) NMR Spectroscopy, and, (B) Molecular Modeling and Simulation. In (A), we will synthesize peptide mimetics of the QPG and PNNP motifs, and perform NMR experiments to ascertain the solution conformational states for these sequence repeats. In (B), we will use computational algorithms to determine low-energy states for polypeptides derived from SM50 motif sequences. Using the structural information obtained from each peptide, we can extrapolate this data to the repeat regions of SM50, which comprise nearly 50% of the protein sequence. Using this "buildup" model, we can then begin to explore how the SM50 structure might "pack" within a calcitic superlattice, or, which regions of the protein may be available for protein-protein association. These approaches should provide us with information regarding the structure of the SM50 intercalation protein, and will eventually pave the way for the rational design of synthetic polymers that will perform the function of intercalation proteins in dental materials.