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Hydroxybenzamide/pyrrole pair distinguishes T·A from A·T base pairs in the minor groove of DNA

Ellervik, Ulf LU orcid ; Wang, Clay C.C. and Dervan, Peter B. (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.

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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 &gt; A &gt;&gt; G &gt; 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}},
}