UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Cytotoxicity and sequence specificity of C- and N-terminus conjugates of N-methylpyrrole polyamides with seco-cyclopropaneindoline

Toth, J; Henry, J; Taherbhai, Z; Staples, T; Summerville, K; Handl, H; Hudson, S; ... Lee, M; + view all (2003) Cytotoxicity and sequence specificity of C- and N-terminus conjugates of N-methylpyrrole polyamides with seco-cyclopropaneindoline. MED CHEM RES , 12 (2) 87 - 93.

Full text not available from this repository.

Abstract

The cytotoxicity and covalent DNA sequence specificity of three novel conjugates of polyamides and seco-cyclopropaneindoline (or seco-CI), a minimum alkylating pharmacophore of CC-1065 are reported. Compounds 1 and 2 consist of a seco-Cl group attached to the C-terminus of either one or two N-methylpyrrole units, respectively. In compound 3, the seco-Cl group is attached to the N-terminus of a one pyrrole-containing analog of distamycin. Following a one-hour exposure of human chronic myeloid leukemia K562 cells, compounds 1 and 2 gave a similar level of cytotoxicity (IC50 1-2 rectangleM). Compound 3 was considerably less active (IC50 >30 rectangleM), despite the fact that it and compound 1 contain one-pyrrole unit each. Using Taq polymerase stop assay, the sequence specificity of the target compounds was determined. Like CC- 1065 and the duocarmycins, compounds 1 and 2 retained the preferential alkylation for the 5'-AAAA(865)A-3' sequence. Compound 3 was less sequence discriminating and showed a preference for alkylation at a 5'-TTTTA(843)-3' sequence over the 5'AAAA(865)A-3' site.

Type: Article
Title: Cytotoxicity and sequence specificity of C- and N-terminus conjugates of N-methylpyrrole polyamides with seco-cyclopropaneindoline
Keywords: PYRINDAMYCIN ALKYLATION SUBUNIT, LEFT-HAND SUBUNIT, DNA-BINDING, COMMON PHARMACOPHORE, CC-1065, ANALOGS, AGENTS, DISTAMYCIN, IDENTIFICATION, MOLECULES
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/99542
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item