Hydroxybenzamide/pyrrole pair distinguishes T·A from A·T base pairs in the minor groove of DNA
(2000) In Journal of the American Chemical Society 122(39). p.9354-9360- Abstract
A new aromatic pair, 2-hydroxy-6-methoxybenzamide/1-methylpyrrole at the terminal position of hairpin polyamides has been designed for distinguishing T·A from A·T base pairs and both from G·C/C·G in the minor groove of DNA. Four eight-ring hairpin polyamides with benzamide (Bz), 2-hydroxybenzamide (Hb-1), 2-hydroxy-6-methylbenzamide (Hb-2), and 2-hydroxy-6-methoxybenzamide (Hb-3) at the N-terminal position were synthesized. The equilibrium association constants (K(a)) were determined at four DNA sites which differ at a single common position, 5'-TNTACA-3' (N = T, A, G, C). Quantitative DNase I footprint titration experiments reveal that (Hb-3)PyPyPy-(R)(H)2(N)γ-ImPyPyPy-β-Dp (4) bound the sequences 5'-TTTACA-3' and 5'-TATACA-3' with... (More)
A new aromatic pair, 2-hydroxy-6-methoxybenzamide/1-methylpyrrole at the terminal position of hairpin polyamides has been designed for distinguishing T·A from A·T base pairs and both from G·C/C·G in the minor groove of DNA. Four eight-ring hairpin polyamides with benzamide (Bz), 2-hydroxybenzamide (Hb-1), 2-hydroxy-6-methylbenzamide (Hb-2), and 2-hydroxy-6-methoxybenzamide (Hb-3) at the N-terminal position were synthesized. The equilibrium association constants (K(a)) were determined at four DNA sites which differ at a single common position, 5'-TNTACA-3' (N = T, A, G, C). Quantitative DNase I footprint titration experiments reveal that (Hb-3)PyPyPy-(R)(H)2(N)γ-ImPyPyPy-β-Dp (4) bound the sequences 5'-TTTACA-3' and 5'-TATACA-3' with high affinity; K(a) = 2.6 x 1010M-1 and K(a) = 8.4 x 109 M-1, respectively, a 3-fold specificity for T vs A was found. Importantly, the sequences 5'-TGTACA-3' and 5'-TCTACA-3' are bound with 50 and 200 times lower affinity, revealing an overall specificity of Hb-3/Py of T > A >> G > C. These results expand the repertoire of sequences targetable by hairpin polyamides.
(Less)
- author
- Ellervik, Ulf LU ; Wang, Clay C.C. and Dervan, Peter B.
- publishing date
- 2000-10-04
- type
- Contribution to journal
- publication status
- published
- in
- Journal of the American Chemical Society
- volume
- 122
- issue
- 39
- pages
- 7 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- scopus:0034605432
- ISSN
- 0002-7863
- DOI
- 10.1021/ja001692u
- language
- English
- LU publication?
- no
- id
- ccd8fc06-a5ef-476c-9d91-23b946a09300
- date added to LUP
- 2023-08-11 08:12:32
- date last changed
- 2024-01-05 04:08:54
@article{ccd8fc06-a5ef-476c-9d91-23b946a09300, abstract = {{<p>A new aromatic pair, 2-hydroxy-6-methoxybenzamide/1-methylpyrrole at the terminal position of hairpin polyamides has been designed for distinguishing T·A from A·T base pairs and both from G·C/C·G in the minor groove of DNA. Four eight-ring hairpin polyamides with benzamide (Bz), 2-hydroxybenzamide (Hb-1), 2-hydroxy-6-methylbenzamide (Hb-2), and 2-hydroxy-6-methoxybenzamide (Hb-3) at the N-terminal position were synthesized. The equilibrium association constants (K(a)) were determined at four DNA sites which differ at a single common position, 5'-TNTACA-3' (N = T, A, G, C). Quantitative DNase I footprint titration experiments reveal that (Hb-3)PyPyPy-(R)(H)2(N)γ-ImPyPyPy-β-Dp (4) bound the sequences 5'-TTTACA-3' and 5'-TATACA-3' with high affinity; K(a) = 2.6 x 10<sup>10</sup>M<sup>-1</sup> and K(a) = 8.4 x 10<sup>9</sup> M<sup>-1</sup>, respectively, a 3-fold specificity for T vs A was found. Importantly, the sequences 5'-TGTACA-3' and 5'-TCTACA-3' are bound with 50 and 200 times lower affinity, revealing an overall specificity of Hb-3/Py of T > A >> G > C. These results expand the repertoire of sequences targetable by hairpin polyamides.</p>}}, author = {{Ellervik, Ulf and Wang, Clay C.C. and Dervan, Peter B.}}, issn = {{0002-7863}}, language = {{eng}}, month = {{10}}, number = {{39}}, pages = {{9354--9360}}, publisher = {{The American Chemical Society (ACS)}}, series = {{Journal of the American Chemical Society}}, title = {{Hydroxybenzamide/pyrrole pair distinguishes T·A from A·T base pairs in the minor groove of DNA}}, url = {{http://dx.doi.org/10.1021/ja001692u}}, doi = {{10.1021/ja001692u}}, volume = {{122}}, year = {{2000}}, }