Collagen Mimetic Structures for Novel Biomaterials

新型生物材料的胶原模拟结构

• 批准号: 0111617
• 负责人: Murray Goodman
• 金额: $ 30万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0111617&HistoricalAwards=false
• 关键词: Collagen; Mimetic; Structures; Novel; Biomaterials

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.

胶原蛋白的研究已成为生物材料技术的一个重要热点。对坚固多样的胶原蛋白生物材料的研究已经扩展到药物输送系统、眼部设备、伤口愈合疗法和人造器官等领域。在Goodman实验室，合成和生物物理策略已经开发出来，设计和研究三螺旋胶原模拟结构作为候选生物材料的特性。作为将N-异丁基甘氨酸（Nleu）纳入胶原蛋白三聚体构建块Gly-Pro-Nleu和Gly-Nleu_Pro的早期工作的扩展，氟化残基氟脯氨酸或N-（六氟）异丁基甘氨酸现在将被纳入三肽构建块。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。生物物理分析包括温度依赖的光学旋转测量，圆二色性（CD）和核磁共振（NMR）光谱，分子建模，以及三螺旋折叠和水合作用的热力学研究。生物特征将由Integra生命科学公司的合作者和加州大学欧文分校的Andrea Tenner小组进行评估。除了新的构建模块，模板已被用于提高三螺旋的稳定性。Tris（羟甲基）氨基甲烷（Tris）已成功衍生创建胶原模拟阵列。额外的胺官能团提供了一个附着在表面和其他活性分子上的点。tris末端的胶原结构将被用于创建双模板分子，其中胶原肽链锚定在N和c端。双模化的胶原蛋白单元可以在链中连接在一起，作为纳米结构（棒状聚合物）形成的前体。根据模板研究，将引入正交保护支架，以组装异三聚体胶原结构，其上可以附着独特的生物相关肽链。这种设计将导致胶原模拟物引发特定的生物反应，以模仿天然胶原蛋白，如胶原I型或防御胶原蛋白C1q。