ORGN 424 |
| The development of a new class of antibiotics is described. This class of C-2 symmetrical macrocyclic compounds traps the Holliday Junction (HJ). The HJ is an intermediate formed during site-specific recombination (which is one of several DNA repair mechanisms). The first generation of our C-2 symmetric macrocyclic compounds was tested in both bacterial growth and biochemical assays. These macrocycles demonstrate accumulation of HJ, that is, they trapped the HJ, and demonstrated bacteria growth inhibition. In addition, these compounds were tested as potential anticancer agents and they have given interesting results in mammalian cancer cell studies. A second generation of macrocyclic peptides is in progress. As with the first generation, linear tripeptides and tetrapeptides are synthesized, dimerized, and finally cyclized. The resulting cyclic hexapeptides and octapeptides are C-2 symmetric, thus matching the HJ head-to-tail symmetry, which has proven to be the binding site for these compounds. This symmetry between ligand and receptor is an important principle in the design of our compounds. |
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Bioorganic, Metal-Mediated Reactions, and Molecular Recognition
8:00 PM-10:00 PM, Tuesday, 30 August 2005 Washington DC Convention Center -- Hall A, Poster
Division of Organic Chemistry |