| EPSRC Reference: |
GR/L88825/01 |
| Title: |
A DYNAMIC MODEL FOR DNA MINOR GROOVE RECOGNITION FROM NMR AND MOLECULAR DYNAMICS SIMULATIONS |
| Principal Investigator: |
Searle, Professor M |
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| Department: |
Sch of Chemistry |
| Organisation: |
University of Nottingham |
| Scheme: |
Standard Research (Pre-FEC) |
| Starts: |
04 January 1999 |
Ends: |
03 January 2000 |
Value (£): |
52,170
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| EPSRC Research Topic Classifications: |
| Biological & Medicinal Chem. |
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| EPSRC Industrial Sector Classifications: |
| No relevance to Underpinning Sectors |
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Summary on Grant Application Form |
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Our understanding of the underlying nature of the intermolecular interactions involved in DNA sequence recognition and their relative importance does not currently enable us to reliably predict the detailed binding characteristics of new ligands. The bis-benzimidazole Hoechst 33258 is an experimental antitumour agent that binds to the minor groove of A-T rich sequences of DNA. X-ray structure determinations of Hoechst 33528-DNA complexes have failed to provide a consistent picture of the mode of recognition of the target sequence, particularly with regard to the drugs primitive degree of G-C recognition. Here we address the question as to whether the balance between electrostatic and steric contributions to sequence selective recognition can explain this complex behaviour, and whether the x-ray structures represent alternative snapshots of a binding mode which really needs to be viewed as dynamic. Using high resolution NMR and state-of-the-art computational methods we plan to examine DNA sequence recognition by two analogues of Hoechst 33258 using time averaged distance restraints versus steric contributions in the recognition of the A-T rich DNA decamer duplex d(GCAAATTTGC)2.
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Key Findings |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Potential use in non-academic contexts |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
| Summary |
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| Date Materialised |
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Sectors submitted by the Researcher |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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| Project URL: |
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| Further Information: |
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| Organisation Website: |
http://www.nottingham.ac.uk |