Binding of a designed anti-cancer drug to the central cavity of an RNA three-way junction

Siriporn Phongtongpasuk; Susann Paulus; Joachim Schnabl; Roland K O Sigel; Bernhard Spingler; Michael J Hannon; Eva Freisinger

doi:10.1002/anie.201305079

Binding of a designed anti-cancer drug to the central cavity of an RNA three-way junction

Angew Chem Int Ed Engl. 2013 Oct 25;52(44):11513-6. doi: 10.1002/anie.201305079. Epub 2013 Aug 23.

Authors

Siriporn Phongtongpasuk¹, Susann Paulus, Joachim Schnabl, Roland K O Sigel, Bernhard Spingler, Michael J Hannon, Eva Freisinger

Affiliation

¹ Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch; School of Chemistry, University of Birmingham, Edgbaston, Birmingham B152TT (UK).

PMID: 24039102
DOI: 10.1002/anie.201305079

Abstract

Getting to the heart of it: Co-crystallization of an RNA three-way junction with a cylindrical di-iron(II)-based anti-cancer drug (green) results in π-stacking interactions between the cylinder and the central base pairs of the RNA structure. The shape, size, and cationic nature of the cylinder were found to be responsible for this perfect fit. Native gel electrophoresis studies confirmed stabilization of the RNA three-way junction by the iron(II) cylinder.

Keywords: RNA recognition; antitumor agents; bioinorganic chemistry; helicates; three-way junctions.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology*
Drug Design
Humans
Models, Molecular
Molecular Structure
Neoplasms / drug therapy*
Nucleic Acid Conformation / drug effects*
RNA / metabolism*

Substances

Antineoplastic Agents
RNA