ORGN 137 |
| The predictable relationship between β-amino acid sequence and folding has inspired several biological applications of β-peptides, including the inhibition of protein-protein interactions. For many such applications it would be desirable to prepare and screen β-peptide libraries. However, standard solid-phase peptide synthesis protocols are not efficient enough to support a library approach, especially for sequences designed to adopt the 14-helix. We have evaluated the effects of microwave irradiation on the solid-phase synthesis of β-peptides, accomplishing a 10-fold reduction in reaction time and improving the initial purity of β-peptide products. Using our optimized microwave reaction conditions, we have synthesized β-peptide libraries in parallel with 96-well filter plates. Our microwave-assisted methodology was adapted to synthesis on polystyrene macrobeads, and we have rapidly prepared high-quality β-peptide combinatorial libraries via split-and-mix techniques. These synthetic methods were applied to the optimization of foldamer inhibitors of the Bcl-xL/BH-3 domain protein-protein interaction. |
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Asymmetric Reactions and Syntheses, Physical Organic Chemistry, Combinatorial Chemistry, Total Synthesis
8:00 PM-10:00 PM, Sunday, 26 March 2006 Georgia World Congress Center -- Ex. Hall B4, Poster
Sci-Mix
Division of Organic Chemistry |