title: 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.
authors.affiliation: Department of Nanobiotechnology, Vision Research Foundation, Chennai, India; Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Centre for Molecular and Medical Research (C-MMR), Faculty of Health, Deakin University, Geelong, Pigdons Road, Waurn Ponds, Geelong, Victoria 3217, Australia; Graduate Student Deakin University (ID: 213510168), Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine, Deakin University, Australia.
authors.forename: Prasanna Kumar
authors.initials: PK
authors.lastname: Athyala
authors.affiliation: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Centre for Molecular and Medical Research (C-MMR), Faculty of Health, Deakin University, Geelong, Pigdons Road, Waurn Ponds, Geelong, Victoria 3217, Australia.
authors.forename: Jagat Rakesh
authors.initials: JR
authors.lastname: Kanwar
authors.affiliation: Bioinformatics Centre, Vision Research Foundation, Chennai, India.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Alameen
authors.affiliation: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Centre for Molecular and Medical Research (C-MMR), Faculty of Health, Deakin University, Geelong, Pigdons Road, Waurn Ponds, Geelong, Victoria 3217, Australia.
authors.forename: Rupinder Kaur
authors.initials: RK
authors.lastname: Kanwar
authors.affiliation: Department of Nanobiotechnology, Vision Research Foundation, Chennai, India.
authors.forename: Subramanian
authors.initials: S
authors.lastname: Krishnakumar
authors.affiliation: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Centre for Molecular and Medical Research (C-MMR), Faculty of Health, Deakin University, Geelong, Pigdons Road, Waurn Ponds, Geelong, Victoria 3217, Australia.
authors.forename: Jon
authors.initials: J
authors.lastname: Watson
authors.affiliation: Bioinformatics Centre, Vision Research Foundation, Chennai, India.
authors.forename: Umashankar
authors.initials: U
authors.lastname: Vetrivel
authors.affiliation: Department of Nanobiotechnology, Vision Research Foundation, Chennai, India. Electronic address: drjrn15@gmail.com.
authors.forename: Janakiraman
authors.initials: J
authors.lastname: Narayanan
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000648:ultrastructure*; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000648:ultrastructure*; D003603:Cytotoxins; D000071858:Epithelial Cell Adhesion Molecule; D008956:Models, Chemical; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods; D009353:Zinostatin / Q000737:chemistry*
chemical_list: D000951:Antigens, Neoplasm; D052157:Aptamers, Nucleotide; D015815:Cell Adhesion Molecules; D003603:Cytotoxins; D000071858:Epithelial Cell Adhesion Molecule; D009353:Zinostatin
keywords: CD spectroscopy; EpCAM aptamer; Insilico modeling; Neocarzinostatin