SPICULE MATRIX MOTIFS--MODEL FOR DENTAL MATERIALS

在牙科医学中，需要新的生物材料用于 骨和牙齿重建与颅面再生术 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质相互作用形成复合材料。 我们的模型系统是海胆针状物，一种矿物基质复合材料 由方解石(CaCO3)和45种基质蛋白质组成的物质。 最近的研究表明，针刺基质蛋白明显 在方解石超晶格中变得“陷落”或嵌入 生物矿化过程。作为这种嵌入的结果， 钙化针状物表现出更强的抗折性。 合成方解石。当确实发生断裂时，“玻璃”断裂特性 都被观察到。这些材料特性非常适合于 牙科材料的应用。我们提出了一个初步的多学科 插层蛋白SM50的研究。我们的目标是确定 -Gln-Pro-Gly-(QPG)和-Pro-Asn-Asn-的三维结构 该蛋白中含有PNNP前序列重复序列。初级阶段 这项研究的工具将是(A)核磁共振光谱，和(B)分子 建模和仿真。在(A)中，我们将合成多肽模拟物 QPG和PNNP基序，并进行核磁共振实验以确定 这些序列重复的溶液构象状态。在(B)项中，我们 将使用计算算法来确定 来源于SM50基序序列的多肽。使用结构 从每个肽中获得的信息，我们可以将这些数据外推到 SM50的重复区，占蛋白质的近50% 序列。使用这个“积聚”模型，我们就可以开始探索 SM50结构可能“堆积”在钙质超晶格中，或者， 蛋白质的区域可能可用于蛋白质-蛋白质的结合。 这些方法应该为我们提供关于 SM50嵌入蛋白的结构，并最终将为 合理设计合成聚合物的方法 插层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.