A Biomimetic Approach to Generating Molecular Diversity

产生分子多样性的仿生方法

• 批准号: 6959260
• 负责人: David A Spiegel
• 金额: $ 4.6万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6959260
• 关键词: bioengineering /biomedical engineering; biomimetics; biotherapeutic agent; chemical genetics; macromolecule; molecular biology; monomer; postdoctoral investigator; small molecule; stereochemistry

DESCRIPTION (provided by applicant): The field of chemical genetics uses small molecules to perturb and study biological systems. In order to obtain a diverse and complex selection of compounds appropriate for chemical genetic analyses, innovative synthetic approaches must be developed. This proposal describes a conceptually novel method for the rapid synthesis of skeletally and stereo chemically diverse small molecule probes, drawing its inspiration from the structural diversity seen in biological macromolecules. To this end, reactive monomers will be assembled into oligomers and subjected to chemical transformations that cause them to "fold" into covalently bonded, rigid structures. Depending upon the identity of the monomers employed and their position within the oligomeric chain, chemical transformation can give rise to skeletally and stereo chemically distinct molecular entities. Proposed small molecule skeletons have been engineered to resemble known natural products with the hope of maximizing compatibility with biological targets. These compounds can be screened against a number of disease states; initial screening efforts will focus on processes relevant to cancer.

描述（由申请人提供）：化学遗传学领域使用小分子干扰和研究生物系统。为了获得适合化学遗传分析的化合物的多样化和复杂的选择，必须开发创新的合成方法。该提案描述了一种概念新颖的方法，用于快速合成立体和立体化学多样性的小分子探针，从生物大分子中看到的结构多样性中汲取灵感。为此，反应性单体将组装成低聚物，并进行化学转化，使它们“折叠”成共价键合的刚性结构。根据所用单体的特性及其在低聚物链中的位置，化学转化可产生立体和立体化学上不同的分子实体。已经将提出的小分子骨架设计成类似于已知的天然产物，希望最大化与生物靶标的相容性。这些化合物可以针对许多疾病状态进行筛选;最初的筛选工作将集中在与癌症相关的过程。