Invasion and Association of Tethered Collagen Mimetics

系留胶原蛋白模拟物的侵袭和结合

• 批准号: 6740360
• 负责人: FRANK W KOTCH
• 金额: $ 4.11万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6740360
• 关键词: biomaterial development /preparation; biomimetics; biotechnology; calorimetry; circular dichroism; collagen; disulfide bond; electron microscopy; infrared spectrometry; molecular assembly /self assembly; peptide chemical synthesis; postdoctoral investigator; protein denaturation; protein sequence; protein structure function; synthetic protein; tissue engineering

DESCRIPTION (provided by applicant): Collagen mimetics will be synthesized and investigated for their ability to (1) undergo strand invasion and to (2) self-assemble into fibrils. In the first aim, the idea of strand invasion in protein mimetics will be tested, i.e. whether a single strand of a collagen mimetic triple helix can be displaced by a tighter binding strand to give a thermodynamically more stable helix. In the proposed study, two tight-binding peptide strands and one weak-binding strand (with a known collagen disease mutation) will be tethered together to nucleate triple helix formation. A single tight-binding strand will then be introduced, and monitored for its ability to displace the weak-binding strand in the helix. In the second aim, mimetics with three tethered tight-binding sequences will be evaluated for their ability to self-associate through intermolecular helix formation to provide stable triple helices that approach the length of natural collagen proteins. To favor self-association, the tether will be shifted so that two strands have overhangs in one direction and the third in the opposite direction. This offset will result in sticky ends for intermolecular association. The long-term goal of these studies is to create novel collagen-based biomaterials of defined properties, structure and size. Experimental results have the potential to shed light on the unknown mechanism of collagen fibril formation, and thus may provide methods of treatment for collagen diseases. Generating large networks of synthetic collagen fibers by the interlocking of small molecules via strand invasion or self-association has numerous potential applications in tissue engineering. Synthetic collagens with defined sequences and fibril sizes are also candidates for alternative matrices for human cell culture.

描述（由申请人提供）：将合成胶原模拟物并研究其（1）经历链侵入和（2）自组装成原纤维的能力。在第一个目标中，将测试蛋白质模拟物中链侵入的想法，即胶原模拟三螺旋的单链是否可以被更紧密的结合链取代，以产生热力学上更稳定的螺旋。在拟议的研究中，两条紧密结合的肽链和一条弱结合链（具有已知的胶原蛋白疾病突变）将被束缚在一起以形成三螺旋形成核。然后将引入单条紧密结合链，并监测其置换螺旋中弱结合链的能力。在第二个目标中，将评估具有三个拴系紧密结合序列的模拟物通过分子间螺旋形成进行自缔合的能力，以提供接近天然胶原蛋白长度的稳定三螺旋。为了有利于自缔合，系链将被移动，使得两条链在一个方向上有突出部分，而第三条链在相反的方向上有突出部分。这种偏移将导致分子间缔合产生粘性末端。这些研究的长期目标是创造具有明确特性、结构和尺寸的新型胶原蛋白生物材料。实验结果有可能揭示胶原纤维形成的未知机制，从而为胶原疾病的治疗提供方法。通过链侵入或自缔合使小分子互锁来生成合成胶原纤维的大型网络，在组织工程中具有许多潜在的应用。具有确定序列和原纤维尺寸的合成胶原蛋白也是人类细胞培养替代基质的候选者。