Peptide self assembly: peptide chemistry effects on nanofiber formation mechanisms and in-gel enzymatic activity

肽自组装：肽化学对纳米纤维形成机制和凝胶内酶活性的影响

• 批准号: 355553-2012
• 负责人: Unsworth, Larry
• 金额: $ 1.75万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572608
• 关键词: Peptide; self; assembly; peptide; chemistry

Self-assembling peptide hydrogels, composed of nanofibers with nanoscale dimensions, are becoming recognized as a robust platform for a variety of applications: delivering active proteins and small molecules. Preliminary studies indicate a lack of immune response or initiation of the coagulation cascade to these materials: the mechanisms of which remain unknown. These properties, plus the ability to precisely control the peptide sequence, and thereby incorporate enzymatic cleavage domains, peptide therapeutics, etc., makes self-assembled peptide hydrogels very attractive. However, it remains apparent that several aspects involved in the design of these materials is ill-defined: effect of peptide chemistry on nanofiber formation, effect of peptide chemistry on vicinal water structure within the hydrogel, subsequent effects on molecular mobility within the hydrogel, in-gel regional viscosities, fundamental mechanisms involved in peptide self assembly, and finally the effect of these factors upon the interaction with a complex biological milieu. Although work has progressed in this area, this grant will build upon what has already been learned over the past 4 years of work supported by the NSERC-Discovery Grant; which has been achieved through the training of two graduate students and several undergraduate researchers. Through understanding the effects of the peptide composition on gel properties as well as protein interactions, it may be possible to develop these materials for multiple technologies: enzymatically controlled drug delivery, tissue engineering scaffolds to enhance wound healing, high surface area biosensors, cardiovascular grafts, etc.

由纳米尺度的纳米纤维组成的自组装肽水凝胶正在成为 被公认为是一个强大的平台，适用于各种应用：递送活性蛋白质和小分子。初步研究表明，这些材料缺乏免疫反应或启动凝血级联反应：其机制仍然未知。这些性质，加上精确控制肽序列的能力，从而掺入酶切割结构域、肽治疗剂等，使得自组装肽水凝胶非常有吸引力。然而，很明显，这些材料的设计中涉及的几个方面是不明确的：肽化学对凝胶形成的影响，肽化学对水凝胶内邻近水结构的影响，随后对水凝胶内分子流动性的影响，凝胶内区域粘度，肽自组装中涉及的基本机制，最后是这些因素对与复杂生物环境相互作用的影响。虽然在这一领域的工作取得了进展，但这笔赠款将建立在过去4年NSERC发现赠款支持的工作中已经学到的东西的基础上;这是通过培训两名研究生和几名本科生研究人员实现的。通过了解肽组合物对凝胶性质以及蛋白质相互作用的影响，有可能开发用于多种技术的这些材料：酶控药物递送、增强伤口愈合的组织工程支架、高表面积生物传感器、心血管移植物等。