Metal-organic compounds as scaffolds for the exploration of biologically relevant chemical space

金属有机化合物作为探索生物相关化学空间的支架

• 批准号: 326972-2008
• 负责人: Luyt, Leonard
• 金额: $ 2.33万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=497837
• 关键词: Metal; organic; compounds; scaffolds; exploration

The objective of this research program is to create metal-peptidomimetics capable of exploring biologically relevant chemical space. Using technetium-99m and rhenium tricarbonyl complexes as a scaffold, we will generate novel means of incorporating these metals into biologically relevant molecules in an integrated fashion. This differs from the traditional approach of a conjugate design, where the pendant metal often has a negative impact on the biological affinity of the ligand. One way to create a metal-peptidomimetic is to use these metals as a turn mimetic, replacing the natural turn region of a peptide. In this fashion the metal becomes hidden within the backbone of the peptide. A second approach is to create metal-peptidomimetic libraries, where the technetium or rhenium core is functionalized to create non-peptidic entities. In this manner the metal serves the purpose of arranging organic ligands in a specific and conformationally locked manner. This program desires to shift technetium and rhenium pharmaceuticals from the era of conjugation chemistry to that of being an integral part of a biologically active molecule.

该研究计划的目标是创造能够探索生物相关化学空间的金属肽模拟物。使用锝-99m和三羰基配合物作为支架，我们将产生新的手段，将这些金属纳入生物相关的分子在一个综合的方式。这不同于传统的缀合物设计方法，其中侧基金属通常对配体的生物亲和力具有负面影响。产生金属-肽模拟物的一种方法是使用这些金属作为转角模拟物，取代肽的天然转角区域。以这种方式，金属变得隐藏在肽的主链内。第二种方法是创建金属肽模拟物文库，其中锝或锝核被官能化以创建非肽实体。以这种方式，金属用于以特定的和构象锁定的方式排列有机配体的目的。该计划旨在将锝和锝药物从共轭化学时代转变为生物活性分子的组成部分。