Poly-proline II (PPII) helices are an important structural motif in mediating protein-protein interactions in multiple signal transduction pathways. Due to their importance, we have focused on developing mimics of the PPII conformation. Proline-templated-amino-acids (PTAA) can be combined using typical peptide synthetic procedures. OligoPTAAs have been shown to adopt the PPII conformation in water. Although, linear synthesis of oligoPTAA allows for the generation of PPII mimic libraries the process is slow as the synthesis of each PTAA requires between eight to fourteen synthetic steps. Our methodology has focused on the development of PTAAs that can be diversified on resin through a specific reaction. Since basic residues are critical to the protein-protein interaction of interest, peptides containing PTAA arginine analogues are our focus. The target was a reaction capable of incorporating substituted guanidine groups onto the PTAA. This would allow the rapid on resin generation of PPII peptide mimetic libraries containing a diverse array of arginine analogs. Although, initially seen as a method applicable to these PPII peptide based libraries it has now found promise in alternative non-peptidic library syntheses.
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