title: 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.affiliation: Department of Chemistry, M. V. Lomonosov Moscow State University, Leninskie Gory 1/3, 119991 Moscow (Russian Federation); Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432 Chernogolovka, Moscow region (Russian Federation). kudr@med.chem.msu.ru.
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Kudryavtsev
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Yu
authors.forename: Polina M
authors.initials: PM
authors.lastname: Ivantcova
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Polshakov
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Churakov
authors.forename: Stefan
authors.initials: S
authors.lastname: Bräse
authors.forename: Nikolay S
authors.initials: NS
authors.lastname: Zefirov
authors.forename: Jih-Hwa
authors.initials: JH
authors.lastname: Guh
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D061565:Cycloaddition Reaction; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011392:Proline / Q000031:analogs & derivatives / Q000737:chemistry; D011487:Protein Conformation; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides; D011392:Proline; D020169:Caspases; C072401:beta-proline
keywords: antiproliferative agents; cycloaddition; mTOR pathway; oligomers; prostate cancer; β-proline