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Probing the biophysical interaction between Neocarzinostatin toxin and EpCAM RNA aptamer.

Abstract
Neocarzinostatin (NCS) a potent DNA-damaging, anti-tumor toxin extracted from Streptomyces carzinostaticus that recognizes double-stranded DNA bulge and induces DNA damage. 2 Fluoro (2F) Modified EpCAM RNA aptamer is a 23-mer that targets EpCAM protein, expressed on the surface of epithelial tumor cells. Understanding the interaction between NCS and the ligand is important for carrying out the targeted tumor therapy. In this study, we have investigated the biophysical interactions between NCS and 2-fluro Modified EpCAM RNA aptamer using Circular Dichroism (CD) and Infra-Red (IR) spectroscopy. The aromatic amino acid residues spanning the β sheets of NCS are found to participate in intermolecular interactions with 2 F Modified EpCAM RNA aptamer. In-silico modeling and simulation studies corroborate with CD spectra data. Furthermore, it reinforces the involvement of C and D1 strand of NCS in intermolecular interactions with EpCAM RNA aptamer. This the first report on interactions involved in the stabilization of NCS-EpCAM aptamer complex and will aid in the development of therapeutic modalities towards targeted cancer therapy.
AuthorsPrasanna Kumar Athyala, Jagat Rakesh Kanwar, Mohamed Alameen, Rupinder Kaur Kanwar, Subramanian Krishnakumar, Jon Watson, Umashankar Vetrivel, Janakiraman Narayanan
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 469 Issue 2 Pg. 257-62 (Jan 08 2016) ISSN: 1090-2104 [Electronic] United States
PMID26642954 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Antigens, Neoplasm
  • Aptamers, Nucleotide
  • Cell Adhesion Molecules
  • Cytotoxins
  • Epithelial Cell Adhesion Molecule
  • Zinostatin
Topics
  • Antigens, Neoplasm (chemistry, ultrastructure)
  • Aptamers, Nucleotide (chemistry)
  • Binding Sites
  • Cell Adhesion Molecules (chemistry, ultrastructure)
  • Cytotoxins
  • Epithelial Cell Adhesion Molecule
  • Models, Chemical
  • Molecular Conformation
  • Molecular Docking Simulation
  • Protein Binding
  • Protein Interaction Mapping (methods)
  • Zinostatin (chemistry)

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