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

• Published in: Chemistry, an Asian journal Vol. 10; no. 2; pp. 383 - 389
• Main Authors: Kudryavtsev, Konstantin V., Yu, Chia-Chun, Ivantcova, Polina M., Polshakov, Vladimir I., Churakov, Andrei V., Bräse, Stefan, Zefirov, Nikolay S., Guh, Jih-Hwa
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.02.2015; WILEY‐VCH Verlag
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; antiproliferative agents; Apoptosis - drug effects; Caspases - metabolism; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; cycloaddition; Cycloaddition Reaction; Humans; Membrane Potential, Mitochondrial - drug effects; mTOR pathway; oligomers; Peptides - chemical synthesis; Peptides - chemistry; Peptides - toxicity; Proline - analogs & derivatives; Proline - chemistry; prostate cancer; Protein Conformation; Stereoisomerism; β-proline; mTOR pathway; prostate cancer; cycloaddition; antiproliferative agents; oligomers; β-proline
• ISSN: 1861-4728; 1861-471X; 1861-471X
• DOI: 10.1002/asia.201403171

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. Oligomers stop proliferation: Cycloadditive oligomerization efficiently produces a set of well‐defined β‐peptides having potent activity for the reduction of growth of prostate cancer cells.