Structural studies and anticancer activity of a novel class of β-peptides.

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.

• Authors: Konstantin V Kudryavtsev, Chia-Chun Yu, Polina M Ivantcova, Vladimir I Polshakov, Andrei V Churakov, Stefan Bräse, Nikolay S Zefirov, Jih-Hwa Guh
• Journal: Chemistry, an Asian journal (Chem Asian J) Vol. 10 Issue 2 Pg. 383-9 (Feb 2015) ISSN: 1861-471X [Electronic] Germany
• PMID: 25408436 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antineoplastic Agents
• Peptides
• Proline
• Caspases
• beta-proline

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, toxicity)
• Apoptosis (drug effects)
• Caspases (metabolism)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cycloaddition Reaction
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Peptides (chemical synthesis, chemistry, toxicity)
• Proline (analogs & derivatives, chemistry)
• Protein Conformation
• Stereoisomerism