PMID: 11310600Apr 20, 2001Paper

Expanding the recognition of the minor groove of DNA by incorporation of beta-alanine in hairpin polyamides

Bioorganic & Medicinal Chemistry
C C WangPeter B Dervan

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)(H2N)gamma-ImPyPyIm-beta-Dp (1) and PyPyPyPy-(R)(H2N)gamma-ImPy-beta-Im-beta-Dp (2) were synthesized which have in common an Py/Im pair in the terminal position for targeting C x G but differ with respect to internal placement of a beta-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)(H2N)gamma-ImPyPyIm-beta-Dp (1) binds the four binding sites with similar affinities, Ka = 1.3-1.9 x 10(10) M(-1) indicating that there is no preference for the position N. In contrast, a redesigned polyamide PyPyPyPy-(R)(H2N)gamma-ImPy-beta-Im-beta-Dp (2) that places an internal flexible aliphatic beta-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 x 10(10) M(-1) and the single base pair mismatch sites with 5- to 25-fold lower affinity). These results expand the repertoire of sequences targetabl...Continue Reading

References

Oct 12, 1987·Nucleic Acids Research·B L Iverson, P B Dervan
Oct 28, 1998·Proceedings of the National Academy of Sciences of the United States of America·L A DickinsonP B Dervan
Dec 22, 1999·Current Opinion in Chemical Biology·P B Dervan, R W Bürli

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Citations

Jul 2, 2003·Current Opinion in Structural Biology·Peter B Dervan, Benjamin S Edelson
Apr 2, 2004·Biological & Pharmaceutical Bulletin·Musti Sree Rama Chandra Murty, Hiroshi Sugiyama
Feb 22, 2012·Analytical Biochemistry·Cynthia M DupureurGaofei He
Jun 15, 2011·Antiviral Research·Terri G EdwardsChris Fisher
May 3, 2012·Medicinal Research Reviews·Chung-Hang LeungDik-Lung Ma
Oct 27, 2015·Future Medicinal Chemistry·Gaofei He, James K Bashkin
May 8, 2016·Biochimie·Elena VasilievaCynthia M Dupureur
Nov 17, 2017·Organic & Biomolecular Chemistry·Beibei LiuW David Wilson
Nov 1, 2011·Chembiochem : a European Journal of Chemical Biology·Ganesh N PandianHiroshi Sugiyama
Aug 27, 2015·Chemistry : a European Journal·Rhys D TaylorHiroshi Sugiyama
Oct 3, 2013·Journal of the American Chemical Society·Yusuke KawamotoHiroshi Sugiyama
Sep 28, 2012·Journal of the American Chemical Society·Jordan L MeierPeter B Dervan
May 14, 2020·Journal of the American Chemical Society·Katsuhiko AbeHiroshi Sugiyama
Feb 8, 2014·Journal of the American Chemical Society·JeenJoo S KangPeter B Dervan
Jan 13, 2018·Chemical Reviews·Alicia J AngelbelloMatthew D Disney
Aug 10, 2019·Journal of the American Chemical Society·Yuki HiroseHiroshi Sugiyama

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