Structural Studies and Anticancer Activity of a Novel Class of β-Peptides

Functionalized oligomeric organic compounds with well-defined beta-proline scaffold have been synthesized by a cycloadditive oligomerization approach in racemic and enantiopure forms. The structure of the novel beta-peptides was investigated by NMR spectroscopic and X-ray methods determining the conformational shapes of the beta-proline oligomers in solution and solid states. The main structural elements subject to conformational switches are beta-peptide bonds between 5-arylpyrrolidine-2-carboxylic acid units ex-isting in Z/E configurations. The whole library of short beta-peptides and intermediate acrylamides has been tested on antiproliferative activity towards the hormone-refractory prostate cancer cell line PC-3 revealing several oligomeric compounds with low micromolar and submicromolar activities. Bromine-substituted dimeric and trimeric acrylamides induced caspase-dependent apoptosis of PC-3 cells through cell-cycle arrest and mitochondrial damage.