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

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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.