ORGN 217 |
| The use of α,α-disubstituted amino acids (ααAAs) to prepare highly helical peptides is well known. Our laboratory is exploring ααAAs in the design of β-sheet peptides. We have now prepared β-hairpin peptides having ααAAs in the i+1 position of the β-turn and shown that these peptides are highly folded in aqueous solution. We are investigating the use of achiral and chiral ααAAs with larger side chains in the sheet portion of hairpin peptides and find that these peptides fold well in aqueous solution. Additionally, ααAA analogues of the hydrophobic core of amyloid β-protein (Aβ). These inhibitors consist of ααAAs incorporated at alternating positions in the sequence. Some of these inhibitors have been effective at preventing Aβ fibrilization at sub-stoichiometric concentrations and they clear amyloid plaques from the brains of transgenic mice that have an Alzheimer's Disease phenotype. Recent results of studies on ααAA-containing peptide synthesis, structure, and function will be presented. |
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Ralph F. Hirschmann Award in Peptide Chemistry
1:30 PM-5:00 PM, Monday, 27 March 2006 Georgia World Congress Center -- C303/304/305, Oral
Division of Organic Chemistry |