© 2004 AAAS
To enhance helicity, protease resistance, and serum stability of BID BH3 peptide, researchers added a, a-disubstituted non-natural amino acids containing olefinic side chains. The substitutions were made to flank three amino acids when placed at position i and i+4, or six amino acids when placed at i and i+7 amino acids, so that reactive olefinic residues would reside on the same face of the a helix. (L.D. Walensky et al.,
Peptide mimetics are becoming increasingly popular pipeline leads for pro-apoptotic cancer drugs. They represent an intriguing way to gain entry to the complex cascades of protein-protein interactions in the cell-death pathway. This is because they can theoretically retain structural and functional properties of native apoptotic proteins, while being small enough to be easily synthesized.
Natural peptides are generally not an option. "Peptides are essentially useless as therapeutic agents," says Gregory Verdine, professor of chemistry ...
