DNA and conclude that (i) an interstrand disulfide cross-link can significantly stabilize duplex DNA while causing little structural distortion; (ii) disulfide cross-links, unlike psoralen,6b do not perturb base pairing and the denaturation pathway of DNA; and (iii) it may be possible to drive structural transitions in DNA and to rationally engineer non-ground-state DNA structures by exploiting the favorable energetics associated with disulfide bond formation. Since these unstrained, intramolecular disulfide bonds are both kinetically and thermodynamically resistant to reduction,27 such cross-linked oligonucleotides should facilitate studies of enzyme-mediated unpairing processes such as transcription, replication, and recombination. Acknowledgment. A.E.F. was supported by NRSA Training Grant GM07598-12. Additional support was provided by the NIH, Hoffmann-La Roche, ICI Pharmaceuticals Group, Bristol-Myers Squibb, and LaJolla Pharmaceuticals. We thank Dr.
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