Expanding the Recognition of the Minor Groove of DNA by Incorporation of β-Alanine in Hairpin Polyamides
Wang, Clay C.C. ; Ellervik, Ulf LU
and Dervan, Peter B.
(2001)
In Bioorganic and Medicinal Chemistry
9(3).
p.653-657
- Abstract
- In order to expand the recognition code by hairpin polyamides to include DNA sequences of the type 5′-CWWC-3′ two polyamides, PyPyPyPy-(R)H2Nγ-ImPyPyIm-β-Dp (1) and PyPyPyPy-(R)H2Nγ-ImPy-β-Im-β-Dp (2) were synthesized which have in common an Py/Im pair in the terminal position for targeting C·G but differ with respect to internal placement of a β-alanine residue. The equilibrium association constants (Ka) 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 the eight-ring hairpin PyPyPyPy-(R)H2Nγ-ImPyPyIm-β-Dp (1) binds the four binding sites with similar affinities, Ka=1.3-1.9×1010M-1 indicating that there is no preference... (More)
- In order to expand the recognition code by hairpin polyamides to include DNA sequences of the type 5′-CWWC-3′ two polyamides, PyPyPyPy-(R)H2Nγ-ImPyPyIm-β-Dp (1) and PyPyPyPy-(R)H2Nγ-ImPy-β-Im-β-Dp (2) were synthesized which have in common an Py/Im pair in the terminal position for targeting C·G but differ with respect to internal placement of a β-alanine residue. The equilibrium association constants (Ka) 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 the eight-ring hairpin PyPyPyPy-(R)H2Nγ-ImPyPyIm-β-Dp (1) binds the four binding sites with similar affinities, Ka=1.3-1.9×1010M-1 indicating that there is no preference for the position N. In contrast, a redesigned polyamide PyPyPyPy-(R)H2Nγ-ImPy-β-Im-β-Dp (2) that places an internal flexible aliphatic β-alanine to the 5′-side of a key imidazole group bound the match site 5′-TCTACA-3′ with high affinity and good sequence discrimination (Ka(match)=4.9×1010M-1 and the single base pair mismatch sites with 5- to 25-fold lower affinity). These results expand the repertoire of sequences targetable by hairpins and emphasize the importance of β-alanine as a key element for minor groove recognition. © 2001 Elsevier Science Ltd. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/73d199b6-888a-4cb0-8686-c9e1a75b5470
- author
- Wang, Clay C.C.
; Ellervik, Ulf
LU
and Dervan, Peter B.
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Bioorganic and Medicinal Chemistry
- volume
- 9
- issue
- 3
- pages
- 653 - 657
- publisher
- Elsevier
- external identifiers
-
- scopus:0035105078
- ISSN
- 0968-0896
- DOI
- 10.1016/s0968-0896(00)00282-0
- language
- English
- LU publication?
- no
- id
- 73d199b6-888a-4cb0-8686-c9e1a75b5470
- date added to LUP
- 2023-08-10 14:46:36
- date last changed
- 2025-04-04 14:47:07
@article{73d199b6-888a-4cb0-8686-c9e1a75b5470,
abstract = {{In order to expand the recognition code by hairpin polyamides to include DNA sequences of the type 5′-CWWC-3′ two polyamides, PyPyPyPy-(R)H2Nγ-ImPyPyIm-β-Dp (1) and PyPyPyPy-(R)H2Nγ-ImPy-β-Im-β-Dp (2) were synthesized which have in common an Py/Im pair in the terminal position for targeting C·G but differ with respect to internal placement of a β-alanine residue. The equilibrium association constants (Ka) 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 the eight-ring hairpin PyPyPyPy-(R)H2Nγ-ImPyPyIm-β-Dp (1) binds the four binding sites with similar affinities, Ka=1.3-1.9×1010M-1 indicating that there is no preference for the position N. In contrast, a redesigned polyamide PyPyPyPy-(R)H2Nγ-ImPy-β-Im-β-Dp (2) that places an internal flexible aliphatic β-alanine to the 5′-side of a key imidazole group bound the match site 5′-TCTACA-3′ with high affinity and good sequence discrimination (Ka(match)=4.9×1010M-1 and the single base pair mismatch sites with 5- to 25-fold lower affinity). These results expand the repertoire of sequences targetable by hairpins and emphasize the importance of β-alanine as a key element for minor groove recognition. © 2001 Elsevier Science Ltd.}},
author = {{Wang, Clay C.C. and Ellervik, Ulf and Dervan, Peter B.}},
issn = {{0968-0896}},
language = {{eng}},
number = {{3}},
pages = {{653--657}},
publisher = {{Elsevier}},
series = {{Bioorganic and Medicinal Chemistry}},
title = {{Expanding the Recognition of the Minor Groove of DNA by Incorporation of β-Alanine in Hairpin Polyamides}},
url = {{http://dx.doi.org/10.1016/s0968-0896(00)00282-0}},
doi = {{10.1016/s0968-0896(00)00282-0}},
volume = {{9}},
year = {{2001}},
}