UDE COBRE: PEPTIDE-BASED BIOMATERIALS WITH ENVIRON SENSITIVE MORPHOLOGIES

UDE COBRE：具有环境敏感形态的肽基生物材料

• 批准号: 7171191
• 负责人: JOEL P SCHNEIDER
• 金额: $ 26.43万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7171191
• 关键词: intermolecular interaction; protein engineering; protein structure function; synthetic protein

We propose to establish a Center of Biomedical Research Excellence (COBRE) at the University of Delaware (UD): Design of l-Iierarebieal Recognition Motifs. Research directives within this center are aimed at developing recognition elements that encompass atomic-level interactions for structural control from small molecules to proteins to mesoscale assemblies. Novel design paradigms will be developed for the study of small molecule-protein interactions, protein assembly in membrane environments, the construction of artificial glycoprotein scaffolds to display multivalent recognition motifs, and the preparation of peptide-based biomaterials whose structures and functions are responsive to environmental cues. Novel synthetic methodology will be pursued to prepare non-natural amino acids for incorporation into proteins to impart unique structure and function. The proposed COBRE center will create an expertise base with appropriate infrastructure that will address biomedical questions by identifying molecular design principles that bear on questions related to the recognition function of biomolecules and the synthetic capability to control molecular topology. Five subprojects will be carried out that incorporate both fundamental and applied research components. All of these projects require detailed information about the interplay of structural motifs. These motifs range from characteristic macromolecular surfaces, domains, and scaffolds to the functional significance of specific amino acid side chain residues. Importantly, design principles established within each individual project can be applied across all of the projects to enhance current design strategies and further the general understanding of biomolecular recognition. The titles of these projects are: I. Small Molecule (z-helix Mimics; II. Peptide-based Biomaterials with Environmentally Sensitive Morphologies; Ill. Strained Molecules for the Synthesis of Unnatural Amino Acids; IV. Artificial Glycoprotein Architectures for Applications in Materials and Biology and V. Determinants of Stability and Assembly of Integral Membrane Proteins. These projects are proposed by recently hired, tenure-track assistant professors in the Department of Chemistry and Biochemistry (DCB) and the Department of Materials Science and Engineering (MSEG). Broadly speaking, projects I and V are in the area of structural biology, and II and IV are in bioengineering through materials. Project III complements these two general areas by developing novel synthetic methodology for the preparation of non-natural amino acids that will elicit new protein structural and functional features. Importantly, the proposed center will serve to integrate the newly established Materials Science and Engineering department and the Organic division of the Chemistry and Biochemistry department into biomedical-related research directives within the University. In addition, this Center will strongly complement not only the Protein Structure Initiative (PSI) launched by the NIH, but also other biomedical research efforts on campus and surrounding institutions. Core facilities to be provided as part of this COBRE will enhance those currently being established on campus and serve to strengthen all of the biomedical research efforts at the University of Delaware.

我们建议在特拉华大学（UD）建立一个生物医学研究卓越中心（COBRE）：L-IierareareBieal识别图案的设计。该中心内的研究指令旨在开发识别元素，这些识别元素涵盖了原子水平的相互作用，以从小分子到蛋白质再到中尺度组件进行结构控制。将开发新的设计范例，用于研究小分子 - 蛋白质相互作用，在膜环境中的蛋白质组装，人工糖蛋白支架的构建以显示多价识别基序以及制备基于肽的生物材料的结构和功能对环境线索有反应。将采用新型的合成方法，以制备非天然氨基酸，以掺入蛋白质中，以赋予独特的结构和功能。拟议的毛线中心将与 适当的基础设施将通过确定与生物分子识别功能有关的问题和控制分子拓扑的合成能力的问题来解决生物医学问题。将进行五个子弹，以结合基本和应用研究组件。所有这些项目都需要有关结构图案相互作用的详细信息。这些基序从特征性的大分子表面，结构域和支架到特定氨基酸侧链残基的功能意义。重要的是，可以在所有项目中应用每个项目中建立的设计原则，以增强当前的设计策略并进一步了解生物分子识别。这些项目的标题是：I。小分子（Z-螺旋模仿； II。基于环境敏感的形态的基于肽的生物材料；疾病的分子，用于合成非自然氨基酸的菌株； iv。iV。人工糖蛋白在材料和生物学中的良好概念和范围的限制均具有范围的概念和范围。雇用的化学和生物化学系（DCB）和材料科学与工程部（MSEG）（MSEG）的雇用助理助理教授。特征。 将新成立的材料科学和工程部和化学和生物化学部的有机部门整合到大学内与生物医学相关的研究指令中。 此外，该中心不仅将不仅补充NIH发起的蛋白质结构倡议（PSI），而且还将在校园和周围机构上发起的其他生物医学研究工作。作为该毛病的一部分提供的核心设施将增强目前在校园内建立的核心设施，并有助于加强特拉华大学的所有生物医学研究工作。