Collagen Mimetic Structures for Novel Biomaterials

胶原蛋白的研究已成为生物材料技术的重要研究热点。对强健和多样化的胶原蛋白生物材料的研究已经扩展到药物输送系统、眼科设备、伤口愈合治疗和人工器官等领域。在古德曼实验室，已经开发了合成和生物物理策略来设计和研究作为候选生物材料的三螺旋胶原模拟结构的性质。作为早期工作的扩展，将N-异丁基甘氨酸(Nleu)加入到胶原蛋白三聚体构建块Gly-Pro-Nleu和Gly-Nleu_Pro中，含氟残基氟脯氨酸或N-(六氟)异丁基甘氨酸现在将被整合到三肽构建块中。它们对三螺旋稳定性的影响将通过一系列生物物理测量来研究。生物物理分析包括依赖于温度的旋光度测量、圆二色谱(CD)和核磁共振(NMR)光谱、分子模拟以及三螺旋折叠和水合的热力学研究。生物档案将由Integra生命科学的合作者和加州大学欧文分校的Andrea Tenner小组评估。除了新的构建块外，模板还被用来增强三螺旋的稳定性。三(羟甲基)氨基甲烷(Tris)已被成功地衍生化成胶原蛋白模拟阵列。附加的胺官能团提供了与表面和其他活性分子的连接点。Tris末端的胶原结构将被用来产生双模板分子，其中胶原多肽链同时锚定在N-末端和C-末端。分散的胶原蛋白单元可以连接成链，作为形成纳米结构(棒状聚合物)的前体。与模板研究相一致，将引入正交保护的支架，以组装可连接独特生物相关肽链的异三聚体胶原蛋白结构。这种设计将产生胶原蛋白模拟物，它能引起对模拟天然胶原蛋白的特定生物反应，如I型胶原蛋白或防御性胶原蛋白C1q。

The area of collagen research has developed into an important focus for biomaterials technology. The search for robust and diverse collagen-based biomaterials has expanded into areas of drug delivery systems, ocular devices, wound healing therapies and artificial organs. In the Goodman laboratories, synthetic and biophysical strategies have been developed to design and investigate the properties of triple helical collagen mimetic structures as candidate biomaterials. %%%As an expansion of early work with n-isobutylglycine (Nleu) incorporated into the collagen trimeric building blocks Gly-Pro-Nleu and Gly-Nleu_Pro, fluorinated residues fluoroproline or N-(hexafluoro)isobutylglycine will now be incorporated into tripeptide building blocks. Their effects on triple-helical stability will be investigated by a series of biophysical measurements. The biophysical analysis includes temperature-dependent optical rotation measurements, circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy, molecular modeling, as well as studies of the thermodynamics of triple helix folding and hydrations. Biological profiles will be assessed by collaborators at Integra Life Sciences and the group of Andrea Tenner at the University of California, Irvine. In addition to novel building blocks, templates have been employed to enhance the stability of triple helices. Tris(hydroxymethyl)aminomethane (TRIS) has been successfully derivatized to create collagen mimetic arrays. The additional amine functional group provides a point of attachment to surfaces and other reactive molecules. The TRIS-terminated collagen structures will be utilized to create ditemplated molecules in which the collagen peptide chains are anchored at both the N- and C-termini. Ditemplated collagen units can be linked together in a chain as precursors for the formation of nanostructures (rod-like polymers). In line with template research, orthogonally protected scaffolds will be introduced in order to assemble heterotrimeric collagen structures to which unique biologically relevant peptide chains can be attached. This design will result in collagen mimetics that elicit specific biological responses to mimic natural collagen proteins such as collagen type I or the defense collagen protein C1q.