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Updated: Jul 7, 2026

In Vitro Chemical Mapping of G-Quadruplex DNA Structures by Bis-3-Chloropiperidines
Published on: May 12, 2023
An asymmetric C8/C8'-tripyrrole-linked sequence-selective pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer DNA
Arnaud C Tiberghien1, David A Evans, Konstantinos Kiakos
1Spirogen Ltd, 29/39 Brunswick Square, London WC1N 1AX, UK.
Abstract:
A novel sequence-selective extended PBD dimer 4 has been synthesized that binds with high affinity to an interstrand cross-linking site spanning 11 DNA base pairs. Despite its molecular weight (984.07) and length, the molecule has significant DNA interstrand cross-linking potency (approximately 100-fold greater than the clinically used agent melphalan) and sub-micromolar cytotoxicity in a number of tumour cell lines, suggesting that it readily penetrates cellular and nuclear membranes to reach its DNA target.
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