Title of article :
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
Author/Authors :
Arnaud C. Tiberghien، نويسنده , , David A. Evans، نويسنده , , Konstantinos Kiakos، نويسنده , , Christopher R.H. Martin، نويسنده , , John A. Hartley، نويسنده , , David E. Thurston، نويسنده , , Philip W. Howard، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2008
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 ( 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.
Keywords :
Cross-linking , Anticancer agent , PBD dimer , Pyrrolobenzodiazepine , Interstrand , PBD , Sequence-selective , DNA-binding
Journal title :
Bioorganic & Medicinal Chemistry Letters
Journal title :
Bioorganic & Medicinal Chemistry Letters
