ORGN 912 |
| b-peptides, with an additional methylene group in the backbone compared to the natural alpha-peptides, are gaining recognition from biological and pharmaceutical standpoints. These peptidomimetics exhibit well-defined secondary structure and possess several other desirable characteristics such as high metabolic stability, long elimination half-lives, cell membrane permeability, and nonmutagenicity. We have recently reported the synthesis of novel b3- and b2-peptides from L-aspartic acid and b-amino L-alanine (L-diaminopropionic acid), respectively [Org. Lett. 2007, 25]. The synthetic methodology involves independent buildup of the peptide backbone and the introduction of sequential side-chain variations leading to a high level of synthetic versatility. Here we report the synthesis of several such b-peptides and their preferred solution conformation using NMR spectroscopy and molecular dynamics simulations. These peptides adopt helical structures in trifluoroethanol and b3-peptides seem to be more structured than the b2-peptides. The metabolic stability of these molecules toward various proteolytic enzymes will also be discussed. |
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Proteins, Peptides, Amino Acids, and Enzyme Inhibitors
8:00 AM-12:00 PM, Thursday, August 23, 2007 BCEC -- 258B, Oral
Division of Organic Chemistry |