Pyrrolobenzodiazepines (PBDs) do not bind to DNA G-quadruplexes

PloS One
Khondaker M RahmanDavid E Thurston


The pyrrolo[2,1-c][1,4] benzodiazepines (PBDs) are a family of sequence-selective, minor-groove binding DNA-interactive agents that covalently attach to guanine residues. A recent publication in this journal (Raju et al, PloS One, 2012, 7, 4, e35920) reported that two PBD molecules were observed to bind with high affinity to the telomeric quadruplex of Tetrahymena glaucoma based on Electrospray Ionisation Mass Spectrometry (ESI-MS), Circular Dichroism, UV-Visible and Fluorescence spectroscopy data. This was a surprising result given the close 3-dimensional shape match between the structure of all PBD molecules and the minor groove of duplex DNA, and the completely different 3-dimensional structure of quadruplex DNA. Therefore, we evaluated the interaction of eight PBD molecules of diverse structure with a range of parallel, antiparallel and mixed DNA quadruplexes using DNA Thermal Denaturation, Circular Dichroism and Molecular Dynamics Simulations. Those PBD molecules without large C8-substitutents had an insignificant affinity for the eight quadruplex types, although those with large π-system-containing C8-substituents (as with the compounds evaluated by Raju and co-workers) were found to interact to some extent. Our molecular...Continue Reading


Nov 1, 1990·Agricultural and Biological Chemistry·H OsadaK Isono
Aug 1, 1970·Journal of Molecular Biology·K W Kohn, C L Spears
Dec 20, 1965·Journal of the American Chemical Society·W LeimgruberJ Berger
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Jan 6, 1999·Biophysical Journal·F FogolariP Viglino
Feb 6, 2002·Chembiochem : a European Journal of Chemical Biology·Jean-Louis Mergny, J C Maurizot
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Jul 28, 2004·The Journal of Biological Chemistry·Dennis GomezJean-François Riou
Feb 25, 2005·Bioorganic & Medicinal Chemistry·Ahmed KamalM Shiva Kumar
Jul 19, 2005·The Journal of Antimicrobial Chemotherapy·Tsveta HadjivassilevaPeter W Taylor
Oct 4, 2005·Journal of Computational Chemistry·David A CaseRobert J Woods
May 23, 2006·Current Medicinal Chemistry·Adnan Salim Abu-Surrah, Mika Kettunen
Oct 3, 2006·Nucleic Acids Research·Sarah BurgeStephen Neidle
Oct 6, 2006·Expert Review of Anticancer Therapy·Robin L Jones, Michael S Ewer
Feb 6, 2007·Biochemistry·Gary N ParkinsonStephen Neidle
Sep 29, 2007·EMBO Reports·Paula BatesDanzhou Yang
May 7, 2008·Journal of the American Chemical Society·Nancy H CampbellStephen Neidle
Dec 23, 2008·Chemical Communications : Chem Comm·Khondaker M RahmanDavid E Thurston
Jan 20, 2009·Anti-cancer Agents in Medicinal Chemistry·Laura CipollaDavide Bini
Mar 12, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniel HochhauserDuncan Jodrell
Apr 25, 2009·Journal of Natural Products·Serge FotsoTaifo Mahmud
Jul 2, 2009·Chemical Communications : Chem Comm·Khondaker M RahmanDavid E Thurston
Aug 13, 2009·Cancer Chemotherapy and Pharmacology·Yelena Y JanjigianNaiyer A Rizvi
Dec 17, 2009·Methods in Molecular Biology·Shozeb Haider, Stephen Neidle
Jun 15, 2010·Medicinal Research Reviews·Barbara Gerratana
Jun 18, 2010·European Journal of Medicinal Chemistry·Ahmed KamalShasi V Kalivendi
Jun 22, 2010·Future Medicinal Chemistry·Danzhou Yang, Keika Okamoto
Nov 26, 2010·Nature Chemistry·Sebastian MüllerShankar Balasubramanian
Dec 21, 2010·Chemical Reviews·Dyeison Antonow, David E Thurston
Jan 22, 2011·Organic & Biomolecular Chemistry·Khondaker M RahmanDavid E Thurston
Feb 25, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Igor PuzanovMace L Rothenberg
Mar 24, 2011·Nucleic Acids Research·Khondaker M RahmanDavid E Thurston
Apr 2, 2011·Nature Reviews. Drug Discovery·Shankar BalasubramanianStephen Neidle
Apr 5, 2011·Expert Opinion on Investigational Drugs·John A Hartley
May 2, 2012·The Journal of Antimicrobial Chemotherapy·Khondaker M RahmanPeter W Taylor
Jul 28, 2012·Chemical Communications : Chem Comm·Khondaker M RahmanDavid E Thurston
Feb 21, 2013·Nature Chemistry·Giulia BiffiShankar Balasubramanian
May 9, 2013·Nature Communications·Enid Yi Ni LamShankar Balasubramanian
Nov 11, 2010·ACS Medicinal Chemistry Letters·Khondaker M RahmanDavid E Thurston


Feb 2, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·George Varvounis
Jun 20, 2019·Journal of Cellular Physiology·Sajad YaghoubiMeghdad Abdollahpour-Alitappeh
Mar 14, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lindsay FergusonFederico Brucoli

Methods Mentioned


Related Concepts

Circular Dichroism, Vibrational
DNA, Double-Stranded
Fluorescence Spectroscopy
Spectrometry, Mass, Electrospray Ionization
Fluorescence Resonance Energy Transfer

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.