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The sequence-specific DNA alkylation by conjugates with an indole linker is examined in the absence or presence of partner Py-Im polyamine. The results have shown that alkylation has proceeded through heterodimer formations, indicating that this is a general way to expand the recognition sequence for DNA alkylation by N-methylpyrrole (Py)-N-methylimidazole (Im) polyamides and 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) conjugates.

The synthesis, DNA alkylating activity and antitumor activity of pyrrole (Py)-imidazole (Im) hairpin polyamide 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CB) conjugates, which contain indole linkers and target C-rich and G-rich strands in double-strand telomere repeat sequences are reported. The analysis has shown that the conjugates have potential as antitumor drugs capable of targeting telomere repeat sequence.

The first example of enantioselective recognition of quadruplex DNA by a chiral cyclic helicene is presented. A new ligand-binding cleft between two telomeric human G-quadruplexes linked by a TTA linker is proposed and it is shown that the cyclic helicene M1 has displayed potent inhibitory activity against telomerase.

The interstrand G-quadruplex structure in the potassium ion solution and the long lariat structure having the same G-quadruplex formation as a model of the T-loop structure are examined. The results have shown that not only strand encroachment but also G-quadruplex formation has stabilized the T-loop structure.

Chiral quaternary structure in a pi-conjugated polymer at room temperature was measured.

Gene silencing was examined by sequence-specific alkylation of DNA by N-methylpyrrole (Py)- N-methylimidazole (Im) hairpin polyamides. Polyamides ImImPyPyγImImPyLDu86 (A) and ImImPyPyγImPyPyLDu86 (B) selectively alkylated the coding regions of the renilla and firefly luciferases, respectively, according to the base pair recognition rule of Py-Im polyamides. Two different plasmids, encoding renilla luciferase and firefly luciferase, were used as vectors to examine the effect of alkylation on gene silencing. Transfection of the alkylated luciferase vectors-by polyamide A or B-into HeLa, 293, and NIH3T3 cells demonstrated that these sequence-specific DNA alkylations lead to selective silencing of gene expression. Next, the vectors were cotransfected into HeLa cells and the cells were treated with polyamide A or B. Selective reduction of luciferase activities was caused by both polyamides. On the basis of this sequence-specific alkylation and gene silencing activity, these alkylating Py-Im polyamides thus have potential as antitumor drugs to target specific gene expression in human cells. [ABSTRACT FROM AUTHOR]