Block co-polymers combining synthetic aqnd biologically based blocks

嵌段聚氨酯是生物医学应用中经常使用的“塑料”，由软硬链段交替不相容的“嵌段”组成。在NSERC先前支持的工作中，我们已经生产了一系列这些聚氨酯，这些聚氨酯专门设计用于包含聚合物内对软组织中天然存在的分子（酶）分解敏感的位点。我们将这些位点置于聚氨酯的硬嵌段中，这是独特的，因为嵌段聚氨酯的降解通常通过软嵌段来控制。 在本申请中，我们建议将我们的注意力转向软段，并掺入通过重组DNA技术产生的天然蛋白质“片段”（多肽）。具体来说，我们将使用基于蛋白质弹性蛋白的多肽。 弹性蛋白存在于弹性的、可伸展的组织如动脉中，并且具有自发自组装成非常小的颗粒和纤维的性质。在利用弹性蛋白作为软段或“塑料”时，我们将能够控制聚氨酯的机械性能、降解速率和生物影响。在第2部分中，我们建议通过设计和表征一系列新型弹性蛋白多肽/聚乙二醇嵌段共聚物系统来扩展弹性蛋白样多肽技术，以产生可用于各种药物递送应用的不同结构。嵌段共聚物形成不同的结构，这取决于亲水性（喜水）嵌段与疏水性（憎水）嵌段的比例。 聚乙二醇是喜水的，而弹性蛋白肽是憎水的。有限数量的研究已经着眼于使用基于生物的共聚物系统。重组技术可用于生产形成不同结构的嵌段共聚物，其具有对药物释放应用重要的特征。此外，这些聚合物系统可能是生物相容的，可能对温度有潜在的反应，并被修饰以将药物递送靶向特定部位。 三名研究生，两名博士和一名硕士以及几名本科论文的学生将支持这项工作。

Segmented polyurethanes, "plastics" frequently used in biomedical applications, are composed of alternating incompatible "blocks" of soft and hard segments. In work previously supported by NSERC,we have produced a family of these polyurethanes specifically designed to contain sites within the polymer that are sensitive to breakdown by molecules that occur naturally in soft tissue, enzymes. We put these sites in the hard block of the polyurethane, unique because the degradation of segmented polyurethanes is typically controlled via the soft block. In this application we propose to turn our attention to the soft segment and incorporate a naturally based protein "fragment" (polypeptide) produced via recombinant DNA technology. Specifically we will use a polypeptide based on the protein elastin. Elastin is found in elastic, extensible tissues such as arteries and has the quality of spontaneous self assembly into very small particles and fibers. In utilising the elastin as the soft segment or the "plastic", we will be able to control the mechanical properties, degradation rate and biological impact of the polyurethane. In part 2, we propose to expand the elastin-like polypeptide technology by designing and characterising a family of novel elastin polypeptide/polyethylene glycol block copolymer systems to produce different structures that can be used in a wide variety of drug delivery applications. Block copolymers form different structures depending on the proportion of hydrophilic (water loving)to hydrophobic(water hating)blocks. Polyethylene glycol is water loving and the elastin-peptide is water hating. A limited number of studies have looked at using biologically based copolymer systems. Recombinant techniques could be used to produce block copolymers that form different structures with characteristics important to in drug release applications. In addition, these polymer system would likely be biocompatible, could potentially respond to temperature and be modified to target the drug delivery to a specific site. Three graduate students, two Ph.D's and one masters as well as several undergraduate thesis students will be supported by this work.