J . Org. Chem. 2000, 65, 5355-5359
5355
Syn th esis a n d Ch a r a cter iza tion of F lu or en on e-, An th r a qu in on e-,
a n d P h en oth ia zin e-La beled Oligod eoxyn u cleotid es: 5′-P r obes for
DNA Red ox Ch em istr y
Mark T. Tierney and Mark W. Grinstaff*
Department of Chemistry, Paul M. Gross Chemical Laboratory, Duke University,
Durham, North Carolina 27708
E-mail: mwg@chem.duke.edu.
Received May 10, 2000
A facile and automated procedure for the synthesis of oligodeoxynucleotides possessing derivatives
of 9-fluoreneone, 9,10-anthraquinone, and phenothiazine is described. The phosphoramidite
approach is used to attach these redox and spectroscopic probes to the 5′-terminus of oligodeoxy-
nucleotides in high yield (>95%). Thermal denaturation studies of labeled oligodeoxynucleotides
show a slight enhancement in duplex stability relative to the unlabeled control, and circular
dichroism spectra confirm B-form helical DNA structure in solution.
In tr od u ction
surface modification techniques affords sensitive devices
(e.g., DNA arrays) for analyzing specific DNA sequences
and gene expression. Although widely used, these
methods require labeling of the target DNA. Electro-
chemical detection of DNA, via an electron-transfer
reaction, offers the benefits of detecting DNA without
prior labeling of the target oligodeoxynucleotides, obtain-
ing high-density arrays, and multiplex electrochemical
sensing.18 Successful reports using daunomycin and
ferrocene labeled oligodeoxynucleotides, as well as other
transition metal and organic mediators, for sensing DNA
are recently described.19-32 In addition, redox and spec-
troscopic probes (e.g., anthraquinone and Ru(dppz)-
(bpy)22+) are currently used to study DNA-mediated
radical cation migration in order to gain mechanistic
insight into oxidative DNA damage.1,2 These basic
studies and analytical applications require an efficient,
high yielding, and reproducible procedure for synthesiz-
ing oligodeoxynucleotides containing well-characterized
reductive and oxidative probes. Herein we describe
Oligodeoxynucleotides possessing probes with unique
spectroscopic and electrochemical properties are of
interest for biophysical studies (electron transfer and
radical cation migration)1-10 and analytical applications
(sequencing and DNA diagnostics).11-17 In the ana-
lytical arena, the use of fluorescently labeled oligo-
deoxynucleotides in conjugation with newly developed
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10.1021/jo0055133 CCC: $19.00 © 2000 American Chemical Society
Published on Web 07/29/2000