Mary L. Kopka

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Recent advances in DNA synthesis methods have made it possible to carry out single-crystal x-ray analyses of double-stranded DNA molecules of predetermined sequence, with 4 to 12 base pairs. At least one example has been examined from each of the three known families of DNA helix: A, B, and Z. Each family has its own intrinsic restrictions on chain folding(More)
Retroviral conversion of single-stranded RNA into double-stranded DNA requires priming for each strand. While host cellular t-RNA serves as primer for the first strand, the viral polypurine tract (PPT) is primer for the second. Therefore, polypurine tracts of retroviruses are essential for viral replication by reverse transcriptase (RT). These purine tracts(More)
The DNA double helix is not a regular, featureless barberpole molecule. Different base sequences have their own special signature, in the way that they influence groove width, helical twist, bending, and mechanical rigidity or resistance to bending. These special features probably help other molecules such as repressors to read and recognize one base(More)
We report the design of optimal linker geometries for the synthesis of stapled DNA-minor-groove-binding molecules. Netropsin, distamycin, and lexitropsins bind side-by-side to mixed-sequence DNA and offer an opportunity for the design of sequence-reading molecules. Stapled molecules, with two molecules covalently linked side-by-side, provide entropic gains(More)
The designed peptide pyridine-2-carboxamidonetropsin (2-PyN) binds to the minor groove of double-helical DNA at two very different sequences, 5'-TTTTT-3' and 5'-TGTCA-3', with comparable energetics but quite different structures. 2-PyN likely binds the 5'-TTTTT-3' site as a 1:l complex, whereas 2-PyN binds 5'-TGTCA-3' sites as a 2:l complex. In order to(More)
  • Milan Mrksicb, Peter B Dervan, S L Tumanyan, V G Gursky, G V Gottikh, B P Dokl +33 others
  • 2001
The two peptides distamycin A (D) and 1-methylimidazole-2-carboxamide-netropsin (2-1") simultaneously bind the five-base-pair sequence 5'-TGTTA-3'. Footprinting experiments indicate that both molecules are necessary for binding to this sequence while affinity cleaving data define the orientations with which each peptide binds to this sequence. The(More)
Bending in double-helical B-DNA apparently occurs only by rolling adjacent base pairs over one another along their long axes. The lifting apart of ends that would be required by tilt or wedge angle contributions is too costly in free energy and does not occur. Roll angles at base steps can be positive (compression of major groove) or negative (compression(More)
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