LIBRARIES OF AMINOGLYCOSIDES AND MIMETICS TARGETING RNA

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Libraries of aminoglycosides and mimetics targeting RNA This project will take rational and combinatorial approaches to develop aminoglycosides and mimetics targeting cancer-associated RNA as well as angiogenesis. It will focus on the following programs: 1. We have discovered that 1,3-hydroxyamines are better than the guanidine groups as recognition motif for the complexation of phosphodiesters and the Hoogsteen face of guanosine in RNA. We will use this new motif as a core to develop small-molecule libraries to screen for inhibitors (using surface plasmon resonance) targeting RNAs and integrins associated with cancer and angiogenesis. 2. Attachment of reactive groups or short antisense deoxyoligonucleotides to the lead candidates to develop sequence selective RNA cleaving agents. Significant contributions in the areas of biomedicine, drug design, drug resistance, synthetic organic chemistry and the discovery of a new generation of anti-cancer agents are expected.