NMR studies of DNA oligomers and their interactions with minor groove binding ligands

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The cationic peptide ligands distamycin and netropsin bind noncovalently to the minor groove of DNA. The binding site, orientation, stoichiometry, and qualitative affinity of distamycin binding to several short DNA oligomers were investigated by NMR spectroscopy. The oligomers studied contain A,T-rich or I,C-rich binding sites, where I = 2-desaminodeoxyguanosine. I{center_dot}C base pairs are functional analogs of A{center_dot}T base pairs in the minor groove. The different behaviors exhibited by distamycin and netropsin binding to various DNA sequences suggested that these ligands are sensitive probes of DNA structure. For sites of five or more base pairs, distamycin can form 1:1 or 2:1 ... continued below

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225 p.

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Fagan, P.A. May 1, 1996.

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  • Fagan, P.A. Lawrence Berkeley National Lab., CA (United States). Structural Biology Div.

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The cationic peptide ligands distamycin and netropsin bind noncovalently to the minor groove of DNA. The binding site, orientation, stoichiometry, and qualitative affinity of distamycin binding to several short DNA oligomers were investigated by NMR spectroscopy. The oligomers studied contain A,T-rich or I,C-rich binding sites, where I = 2-desaminodeoxyguanosine. I{center_dot}C base pairs are functional analogs of A{center_dot}T base pairs in the minor groove. The different behaviors exhibited by distamycin and netropsin binding to various DNA sequences suggested that these ligands are sensitive probes of DNA structure. For sites of five or more base pairs, distamycin can form 1:1 or 2:1 ligand:DNA complexes. Cooperativity in distamycin binding is low in sites such as AAAAA which has narrow minor grooves, and is higher in sites with wider minor grooves such as ATATAT. The distamycin binding and base pair opening lifetimes of I,C-containing DNA oligomers suggest that the I,C minor groove is structurally different from the A,T minor groove. Molecules which direct chemistry to a specific DNA sequence could be used as antiviral compounds, diagnostic probes, or molecular biology tools. The author studied two ligands in which reactive groups were tethered to a distamycin to increase the sequence specificity of the reactive agent.

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225 p.

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OSTI as DE96013947

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  • Other Information: TH: Thesis (Ph.D.)

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  • Other: DE96013947
  • Report No.: LBNL--39118
  • Grant Number: AC03-76SF00098
  • Office of Scientific & Technical Information Report Number: 373863
  • Archival Resource Key: ark:/67531/metadc683542

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Office of Scientific & Technical Information Technical Reports

Reports, articles and other documents harvested from the Office of Scientific and Technical Information.

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  • May 1, 1996

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  • July 25, 2015, 2:20 a.m.

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  • Aug. 24, 2016, 1:38 p.m.

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Fagan, P.A. NMR studies of DNA oligomers and their interactions with minor groove binding ligands, thesis or dissertation, May 1, 1996; California. (digital.library.unt.edu/ark:/67531/metadc683542/: accessed October 21, 2017), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.