Femtogenix illustrates the potential of pyrrolobenzodiazepine (PBD) monomeric conjugates and dimers to bind to terminal guanine bases of DNA

Femtogenix co‑authored a research article on 7th April 2016 entitled ‘Covalent Bonding of Pyrrolobenzodiazepines (PBDs) to Terminal Guanine Residues within Duplex and Hairpin DNA Fragments’.

PBD molecules were traditionally thought to require a DNA triplet (e.g., 5’‑AGA‑3’) to bind to DNA. Through HPLC, MS‑MS and molecular dynamics simulation experiments, researchers demonstrated that PBD dimers and the C8‑conjugated PBD monomer GWL‑78 can covalently bond to a terminal guanine base of DNA (therefore only requiring two base pairs), whereas the PBD monomer anthramycin failed to do so. This highlighted the importance of PBD C8‑substituents in assisting recognition of DNA, and suggested the PBDs have a potential novel mechanism of action of DNA strand breakage at terminal guanines, which may have clinical importance.

The full article is accessible via the following link: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152303