Bioorganic Chemistry
13
Fig. 9
PNA: peptide nucleic
acid, a synthetic polynucleotide
with an amide backbone.
O
N
HN
Base
O
O
N
O
Base
HN
O
the hybridized PNA is greater relative to
its DNA analog.
In addition to alterations in the back-
bone, numerous bioorganic investigations
have examined the effect of novel bases
incorporated into DNA. (Many of these
studies would be impossible without the
prior development of efFcient solid-phase
oligonucleotide synthesis.) ±or example,
Kool and coworkers have incorporated
steric analogs of the nucleoside bases that
have the same shape as the normal bases
but have no hydrogen bonding capability.
Difluorotoluene (±ig. 10) closely mimics
the shape of thymine but is nonpolar and
does not closely mimic its charge prop-
erties. Despite this, it can efFciently and
speciFcally direct the incorporation of ade-
nine opposite to it by DNA polymerase
when it is used in oligonucleotides. This
kind of result helps tease apart the relative
importance of charge and shape in molec-
ular recognition processes.
3.2
Small Molecules
There are
literally hundreds
of small
molecules that have been found to have
interesting
or
useful
effects
that
de-
pend upon their binding to DNA and
form the basis for bioorganic investi-
gations. The uses of these compounds
include (1) antiviral and antineoplastic (an-
ticancer) chemotherapies (e.g. bleomycin),
(2) nucleotide stains (e.g. ethidium bro-
mide), and (3) biochemical probes for
nucleic acid structure (e.g. phenanthro-
line complexes). The major interaction
modes are binding to the minor and major
grooves,
intercalation
between
stacked
base pairs, as well as a host of potential
Fig. 10
Comparison of thymine
and its steric analog
difluorotoluene.
N
NH
O
O
O
HO
HO
Thymine
F
F
O
HO
HO
Thymine steric mimic:
difluorotoluene
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