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Structural Studies and Anticancer Activity of a Novel Class of β‐Peptides
Authors:Prof. Dr. Konstantin V. Kudryavtsev  Chia‐Chun Yu  Polina M. Ivantcova  Prof. Dr. Vladimir I. Polshakov  Dr. Andrei V. Churakov  Prof. Dr. Stefan Bräse  Prof. Dr. Nikolay S. Zefirov  Prof. Dr. Jih‐Hwa Guh
Affiliation:1. Department of Chemistry, M.?V. Lomonosov Moscow State University, Leninskie Gory 1/3, 119991 Moscow (Russian Federation);2. Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432 Chernogolovka, Moscow region (Russian Federation);3. School of Pharmacy, National Taiwan University, No.1, Sect. 1, Jen‐Ai Rd, Taipei 100 (Taiwan);4. Faculty of Fundamental Medicine, M.?V. Lomonosov Moscow State University, 119991 Moscow (Russian Federation);5. Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Leninskii prosp. 31, 119991 Moscow (Russian Federation);6. Institute of Organic Chemistry (IOC), Karlsruhe Institute of Technology (KIT), Fritz‐Haber‐Weg 6, 76133 Karlsruhe (Germany);7. Institute of Toxicology and Genetics (ITG), Karlsruhe Institute of Technology (KIT), Eggenstein‐Leopoldshafen (Germany)
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.
Keywords:antiproliferative agents  cycloaddition  mTOR pathway  oligomers  prostate cancer  β  ‐proline
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