2. Academic Validation
  3. An asymmetric C8/C8'-tripyrrole-linked sequence-selective pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer DNA interstrand cross-linking agent spanning 11 DNA base pairs

An asymmetric C8/C8'-tripyrrole-linked sequence-selective pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer DNA interstrand cross-linking agent spanning 11 DNA base pairs

  • Bioorg Med Chem Lett. 2008 Mar 15;18(6):2073-7. doi: 10.1016/j.bmcl.2008.01.096.
Arnaud C Tiberghien 1,  David A Evans,  Konstantinos Kiakos,  Christopher R H Martin,  John A Hartley,  David E Thurston,  Philip W Howard
Affiliations

Affiliation

  • 1 Spirogen Ltd, 29/39 Brunswick Square, London WC1N 1AX, UK.
PMID: 18272367 DOI: 10.1016/j.bmcl.2008.01.096
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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