Structural studies and anticancer activity of a novel class of β-peptides
Journal
Chemistry - An Asian Journal
Journal Volume
10
Journal Issue
2
Pages
383-389
Date Issued
2015
Author(s)
Abstract
Functionalized oligomeric organic compounds with well-defined β-proline scaffold have been synthesized by a cycloadditive oligomerization approach in racemic and enantiopure forms. The structure of the novel β-peptides was investigated by NMR spectroscopic and X-ray methods determining the conformational shapes of the β-proline oligomers in solution and solid states. The main structural elements subject to conformational switches are β-peptide bonds between 5-arylpyrrolidine-2-carboxylic acid units existing in Z/E configurations. The whole library of short β-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. ? 2015 Wiley-VCH Verlag GmbH & Co. KGaA.
Subjects
Antiproliferative agents; Cycloaddition; mTOR pathway; Oligomers; Prostate cancer; β-proline
SDGs
Other Subjects
Cell culture; Cell death; Cycloaddition; Diseases; Organic polymers; Peptides; Urology; Anti-proliferative activities; Anticancer activities; Antiproliferative agents; Conformational switches; Mitochondrial damage; mTOR pathway; Prostate cancer cells; Prostate cancers; Oligomers; antineoplastic agent; beta-proline; caspase; peptide; proline; analogs and derivatives; apoptosis; cell cycle checkpoint; chemistry; cycloaddition; drug effects; human; metabolism; mitochondrial membrane potential; protein conformation; stereoisomerism; synthesis; tumor cell line; Antineoplastic Agents; Apoptosis; Caspases; Cell Cycle Checkpoints; Cell Line, Tumor; Cycloaddition Reaction; Humans; Membrane Potential, Mitochondrial; Peptides; Proline; Protein Conformation; Stereoisomerism
Type
journal article