Grant: Discovery Grants Program - Individual

Bioorganic Chemistry/Chemical Biology: Trainees synthesize new entities that address fundamental mechanistic aspects of catalysis as well as exhibit novel and exciting properties for practical applications in biotechnology and medicine. The major questions we will pursue are: 1)Chemically Modified DNAzyme catalysts that have an enhanced chemical repertoire for sensing glycosides, penetrating cell membranes, and utilizing important metals (e.g. Fe2+), for catalysis. To do this we will build on our previous work by preparing synthetically modified dNTPs that present extra functionalities (e.g. boronic acids, polyamines, long-chain aliphatic amides, carboxylates, and phenolates). 2)Studying the basic fundamental aspects of RNA catalysis with particular regards to the ribosome and the glm-S ribozyme. We broadened our interests in the fundamental aspects of ribozymes catalysis by developing new active-site probes for general acid and base catalysis. Here we will study the ribosome and new ribo-switches with a long term goal of adding mechanistic insight as the mechanism of action and to develop an ""RNAomic"" approach to identifying new ribozymes in cells. 3)Exploring heterocycles with extended H-bonding complementarity for duplex DNA recognition and nanostructured DNA-inspired materials. Our publication on self-complementary H-bonding heterocycles provide important synthetic precursors and uniquely equips us to oligomerize these heterocycles for synthetic DNA recognition. 4)Synthetic approaches to Amanitin and other related Natural Products. Our publications on controlled tryptophan oxidation enable a rapid and simple entrée into several classes of natural products including the phakellistatins, omphalotins, phalloidins and amanitins with both directed and combinatorial libraries thereof. Trainees master a wide knowledge of both fundamental principles in physical, biological and synthetic organic chemistry as applied to important biological questions.