AN ASYMMETRIC CYANINE DYE BINDING IN THE MINOR GROOVE
OF DNA
Jonas Karlsson1, Per Lincoln2 and Gunnar Westman1
1Organic
2Physical
Chemistry, Chalmers University of Technology
Chemistry, Chalmers University of Technology
Asymmetric cyanine dyes have achieved much interest recently due to their
excellent properties as non-covalent labels for nucleic acids. Upon binding to
nucleic acids these dyes exhibit a very large enhancement in fluorescence
intensity and have been used as fluorescent markers for DNA in various
contexts. The cyanine dyes TO, BO and YO binds by intercalation between the
bases in a non-specific fashion towards DNA-sequences. Furthermore they also
have a strong affinity for single stranded DNA with a large increase in
fluorescence upon binding. This makes the dyes less useful in studies where
only a signal from double stranded DNA is desirable.
N
N
X
S
TO: X = S
N
YO: X = O
BO
N
We here report synthesis and studies of the first asymmetric cyanine dye 1
binding in the minor groove of DNA instead of by intercalation. The
extraordinary fluorescence properties of the intercalating cyanine dyes are
retained in this groove binding dye. Ligands binding in the minor groove e. g.,
Hoechst and DAPI have some advantages as fluorescent markers for DNA
compared to the intercalating cyanine dyes e. g.; a DNA-sequence selectivity,
an ability to distinguish double from single stranded DNA and a smaller
perturbation of the DNA-duplex upon binding. However, they don’t exhibit an
equally dramatic increase in fluorescence upon binding to DNA as that of the
asymmetric cyanine dyes. A dye that combines the features of the minor groove
binding ligands and the photophysical properties of the ordinary asymmetric
cyanine dyes would thus be of great value in detection and studies of nucleic
acids. Studies are underway to investigate the scope of this new cyanine dye 1.
N
N
S
S
1
N