Wells, G., Martin, C.R.H., Howard, P.W., Sands, Z.A., Laughton, C.A., Tiberghien, A.C., Woo, C.-K., Masterson, L., Stephenson, M.J., Hartley, J.A., Jenkins, T.C., Shnyder, S.D., Loadman, P.M., Waring, M.J. and Thurston, D.E. (2006) Design, synthesis and biophysical and biological evaluation of a series of pyrrolobenzodiazepine-poly(N-methylpyrrole) conjugates. Journal of Medicinal Chemistry, 49 (18). pp. 5442-5461. 10.1021/jm051199z .
Full text not available from this repository.
A novel series of methyl ester-terminated C8-linked pyrrolobenzodiazepine (PBD)-poly(N-methylpyrrole) conjugates (50a-f) has been synthesized and their DNA interaction evaluated by thermal denaturation, DNA footprinting, and in vitro transcription stop assays. The synergistic effect of attaching a PBD unit to a polypyrrole fragment is illustrated by the large increase in DNA binding affinity (up to 50-fold) compared to the individual PBD and pyrrole components. 50a-f were found to bind mainly to identical DNA sequences but with apparent binding site widths increasing with molecular length and the majority of sites conforming to the consensus motif 5'-XGXWz (z = 3 ± 1; W = A or T; X = any base but preferably a purine). They also provided robust sequence-selective blockade of transcription at sites corresponding approximately to their DNA footprints. 50a-f were shown to have good cellular/nuclear penetration properties, and a degree of correlation between cytotoxicity and DNA-binding affinity was observed.
|Additional Information:||Full text available in print and electronically from the School of Pharmacy Library.|
|Departments, units and centres:||Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry|
|Journal or Publication Title:||Journal of Medicinal Chemistry|
|Deposited By:||Library Staff|
|Deposited On:||20 May 2008 15:04|
|Last Modified:||12 May 2011 12:59|
Item downloaded times since 20 May 2008 15:04.
Repository Staff Only: Item control page
School of Pharmacy Staff Only: Edit a copy to replace this item