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Energetic basis for selective recognition of T center dot G mismatched base pairs in DNA by imidazole-rich polyamides

Lacy, ER; Nguyen, B; Le, M; Cox, KK; O'Hare, C; Hartley, JA; Lee, M; (2004) Energetic basis for selective recognition of T center dot G mismatched base pairs in DNA by imidazole-rich polyamides. NUCLEIC ACIDS RES , 32 (6) 2000 - 2007. 10.1093/nar/gkh515. Gold open access

Abstract

To complement available structure and binding results and to develop a detailed understanding of the basis for selective molecular recognition of T.G mismatches in DNA by imidazole containing polyamides, a full thermodynamic profile for formation of the T.G-polyamide complex has been determined. The amide-linked heterocycles f-ImImIm and f-PyImIm (where f is formamido group, Im is imidazole and Py is pyrrole) were studied by using biosensor-surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) with a T.G mismatch containing DNA hairpin duplex and a similar DNA with only Watson-Crick base pairs. Large negative binding enthalpies for all of the polyamide-DNA complexes indicate that the interactions are enthalpically driven. SPR results show slower complex formation and stronger binding of f-ImImIm to the T.G than to the match site. The thermodynamic analysis indicates that the enhanced binding to the T.G site is the result of better entropic contributions. Negative heat capacity changes for the complex are correlated with calculated solvent accessible surface area changes and indicate hydrophobic contributions to complex formation. DNase I footprinting analysis in a long DNA sequence provided supporting evidence that f-ImImIm binds selectively to T.G mismatch sites.

Type: Article
Title: Energetic basis for selective recognition of T center dot G mismatched base pairs in DNA by imidazole-rich polyamides
Open access status: An open access publication
DOI: 10.1093/nar/gkh515
Keywords: MINOR-GROOVE LIGANDS, MOLAR HEAT-CAPACITY, VANT-HOFF, B-DNA, SIGNIFICANT DISCREPANCIES, CALORIMETRIC ENTHALPIES, CIRCULAR-DICHROISM, HAIRPIN POLYAMIDE, BINDING, THERMODYNAMICS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/125788
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