1 research outputs found
Specific Alkylation of Human Telomere Repeat Sequences by a Tandem-Hairpin Motif of Pyrrole–Imidazole Polyamides with Indole-<i>seco</i>-CBI
We designed and synthesized a tandem-hairpin
motif of pyrrole (P)î—¸imidazole
(I) polyamide 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3<i>H</i>-benzÂ[e]Âindole (<i>seco</i>-CBI) conjugates (<b>1</b>) that targets the human telomere repeat sequence 5′-dÂ(CCCTAA)<sub><i>n</i></sub>-3′. As a control, conjugate <b>2</b> (hairpin PI polyamide with <i>seco</i>-CBI), which
also targets the human telomere repeat sequence, was synthesized.
High-resolution denaturing polyacrylamide gel electrophoresis (PAGE)
using 5′ Texas Red-labeled 219-bp DNA fragments revealed the
outstandingly high sequence selectivity of <b>1</b>, with no
mismatch alkylation. Furthermore, an evaluation performed in human
cancer cell lines demonstrated that conjugate <b>1</b> has low
cytotoxicity compared with conjugate <b>2</b>. In addition,
a cell-staining analysis indicated that conjugate <b>1</b> induced
apoptosis moderately by DNA damage. This study demonstrated that conjugate <b>1</b> can be used as an effective alkylator for telomere repeat
sequences or as an apoptotic inducer