ORGN 738 |
Synthesis and evaluation of novel chiral aaAAs as b-sheet stabilizing factors
| Jia Wang and Robert P. Hammer. Department of Chemistry, Louisiana State University, 232 Choppin Hall, Baton Rouge, LA 70803 |
| A number of diseases including Alzheimer's disease and the prion disease are caused by protein misflolding into b-sheet structures. An increased understanding of what factors control or stabilize b-sheet structures may lead to insights to the underlying causes of these diseases and suggest possible treatments for such protein misfolding disorders. Modeling studies suggest that chiral Ca,a disubstituted amino acids (aaAA) can stabilize b-strand conformations and may also create additional stabilizing intrastrand and interstrand side-chain interactions for sheet-like structures. In our study, several chiral aaAAs have been synthesized by using a chiral phase transfer catalyst as shown below. The enantiomeric excess of each amino acid was determined by 19F-NMR analysis of the Mosher amide and/or chiral HPLC. These chiral aaAAs have been incorporated into the hydrogen bonding positions of model b-sheet peptides containing a disulfide. Thermodynamic analyses of the structural effects of aaAAs on b-hairpin formations are determined by the ratio of [dithiol] to [disulfide] as compared to a standard (Glutathione/Glutathione disulfide). 
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Proteins, Peptides, and Amino Acids
8:00 AM-12:00 PM, Thursday, August 26, 2004 Pennsylvania Convention Center -- 201A, Oral
Division of Organic Chemistry
The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004
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