Metallo-oligodeoxynucleotides and DNA-Mediated Charge Transfer

Oligodeoxynucleotides (ODNs) modified with functional reporter groups have diverse and important research and clinical applications including primers for DNA sequencing, hybridization probes for detecting DNA, anti-sense and antigene oligonucleotides for therapy, and spectroscopic probes for DNA structure and function studies. We have developed synthetic strategies to site-specifically label ODNs with spectroscopic and/or redox-active transitional metal or organic chromophores. The first approach involves synthesizing the labeled phosphoramidite for subsequent incorporation into the nucleic acid strand using standard DNA synthesis protocols (see Figure). The second approach entails derivatizing the ODN during solid-phase synthesis using Pd(0) cross-coupling chemistry (see Figure). In DNA the effects of oligodeoxynucleotide sequence, base-pairing, p-stacking, as well as the donor-acceptor distance and driving force on electron-transfer rates are of interest, and experiments are being performed to address many of these issues. Using our synthetic skills, we have prepared DNA duplexes labeled with electron-transfer probes. We observed an electron-transfer reaction between phenothiazine (PTZ), the electron donor, and the photoexcited acceptor chromophore, *Ru(bpy)2(4-m-4'-pa-bpy)2+.flaps.

Selected Publications

“Synthesis and Characterization of p-Stacked Phenothiazine Oligodeoxynucleotides.”
S. A. Nadeem Hashmi, Xi Hu, Chad E. Immoos, Stephen J. Lee, and Mark W. Grinstaff
Organic Letters, 2002, 4, 4571-4574. Link
“Synthesis, Thermodynamics, and Photophysics of Phenothiazine Labeled Oligodeoxynucleotides: Novel 2’-Deoxyadenosine and Thymidine Ribose Probes for Labeling DNA.”
Xi Hu, Mark T. Tierney, and Mark W. Grinstaff
Bioconjugate Chemistry, 2002, 13, 83-89. Link
“Synthesis and Stability of Oligodeoxynucleotides Containing C8-Labeled 2-Deoxyadenosine: Novel Redox Nucleobase Probes for DNA Mediated Charge-Transfer Studies.”
Mark T. Tierney and Mark W. Grinstaff
Organic Letters, 2000, 2, 3413-3416. Link
“Synthesis and Characterization of Fluorenone, Anthraquinone, and Phenothiazine Labeled Oligodeoxynucleotides: 5'-Redox Probes for DNA Redox Chemistry.”
Mark T. Tierney and Mark W. Grinstaff
Journal of Organic Chemistry, 2000, 65, 5355-5359. Link
“Electron Transfer in an Oligonucleotide Duplex: Observation of the Electron-Transfer Intermediate.”
Mark T. Tierney, Milan Sykora, Shoeb I. Khan, and Mark W. Grinstaff
Journal of Physical Chemistry B, 2000, 104, 7574-7576. Link
“On-Column Derivatization of Oligodeoxynucleotides with Ferrocene.”
Amy E. Beilstein and Mark W. Grinstaff
Chemical Communications, 2000, 509-510. Link
“Solid-Phase Synthesis and Photophysical Properties of DNA Labeled at the Nucleobase with Ru(bpy)2(4-m-4'-pa-bpy)2+.”
Shoeb I. Khan, Amy E. Beilstein, Milan Sykora, Gregory D. Smith, and Mark W. Grinstaff
Inorganic Chemistry, 1999, 38, 5999-6002.
“How Do Charges Travel in DNA?”
Mark W. Grinstaff
Angewante Chemie International Edition, 1999, 38, 3629-3635 (invited highlight). Link
“Automated Solid-Phase DNA Synthesis and Photophysical Properties of Oligonucleotides Labeled at the 5'-Terminus with Ru(bpy)32+.”
Shoeb I. Khan, Amy E. Beilstein, Milan Sykora, Gregory D. Smith, Xi Hu, and Mark W. Grinstaff
Inorganic Chemistry, 1999, 38, 3922-3925. Link
“Synthesis and Excited-State Properties of a Novel Ruthenium Nucleoside: Ru(bpy)2(5-bpy-2'-deoxyuridine)2+.”
Shoeb I. Khan, Amy E. Beilstein, Gregory D. Smith, Milan Sykora, and Mark W. Grinstaff
Inorganic Chemistry, 1999, 38, 2411-2415. Link
“Palladium(0) Catalyzed Modification of Oligonucleotides during Automated Solid-Phase Synthesis.”
Shoeb I. Khan and Mark W. Grinstaff
Journal of the American Chemical Society, 1999, 121, 4704-4705. Link
“Automated Solid-Phase Synthesis of Site Specifically Labeled Ruthenium-Oligonucleotides.”
Shoeb I. Khan, Amy E. Beilstein, and Mark W. Grinstaff
Inorganic Chemistry, 1999, 38, 418-419. Link