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Title of article :
Sequence specific recognition of DNA by tailor-made hairpin conjugates of achiral seco-cyclopropaneindoline-2-benzofurancarboxamide and pyrrole–imidazole polyamides
Author/Authors :
Carly A. Price، نويسنده , , Brian M. Lingerfelt، نويسنده , , Heather L. Handl، نويسنده , , Konstantinos Kiakos، نويسنده , , John A. Hartley، نويسنده , , Moses Lee، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2005
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Abstract :
Hairpin conjugates of achiral seco-cyclopropaneindoline-2-benzofurancarboxamide (achiral seco-CI-Bf) and three diamides (ImPy 1, PyIm 2, and PyPy 3, where Py is pyrrole, and Im is imidazole), linked by a γ-aminobutyrate group, were synthesized. The sequence-specific covalent alkylation of the achiral CI moiety with adenine-N3 in the minor groove was ascertained by thermally induced DNA cleavage experiments. The results provide evidence that hairpin conjugates of achiral seco-CI-Bf-γ-polyamides could be tailored to target specific DNA sequences according to a set of general rules: the achiral CI moiety selectively reacts with adenine-N3, a stacked pair of imidazole/benzofuran prefers a G/C base pair, and a pyrrole/benzofuran prefers an A/T or T/A base pair. Models for the binding of hairpin conjugates 1–3 with sequences 5′-TCA(888)G-3′, 5′-CAA(857)C-3′, and 5′-TTA(843)C-3′ are proposed.
Keywords :
Duocarmycins , polyamides , DNA , Sequence specificity , Conjugates
Journal title :
Bioorganic & Medicinal Chemistry Letters
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