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

这项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多肽模拟物。利用~(99)Tm和~(99)Re的三羰基络合物作为支架，我们将产生一种新的方法，将这些金属以集成的方式结合到生物相关的分子中。这不同于传统的共轭设计方法，在传统方法中，悬挂金属经常对配体的生物亲和力产生负面影响。制造金属模拟多肽的一种方法是使用这些金属作为转位模拟物，取代多肽的自然转位区域。以这种方式，金属就隐藏在多肽的主干中。第二种方法是创建模拟金属多肽的文库，在该文库中，锶或铼的核心被功能化，以创建非肽实体。以这种方式，金属用于以特定和构象锁定的方式排列有机配体的目的。该计划希望将氚和铼药物从结合化学时代转变为生物活性分子不可分割的一部分。

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.