Chemistry Reference
In-Depth Information
1
Sequence - Selective Binding of
Transition Metal Complexes to DNA
Einar Sletten and Nils Å ge Fr ø ystein
1.1 Introduction
The biological signifi cance of the interaction between metal ions and nucleic acids
has become a rather well-established fact. One may mention the observed necessity
for the presence of metal ions in many natural processes where nucleic acids play
the dominant role. The effect of platinum-based chemotherapeutic drugs probably
originates from their attack on DNA. Another aspect of metals in biological systems
is the increased fl ux of metals in the environment during the last decades. An assess-
ment of the toxic effect of an unnatural metal ion concentration must include
information on the processes in which the metal can participate. In a comparison
of metal carcinogenicity in humans based on several experimental factors, Cr and
Ni turned out to be the most potent carcinogens.
1
The nucleic acid monomers, guanine (G), adenine (A), thymine (T) and cyto-
sine (C) have different metal ion affi nities. The order of stability of 3d transition
metal ion-nucleobase complexes are: G
T .
2
At physiological pH the pre-
ferred binding sites on the nucleobases are: guanine N7, adenine N1 and/or N7,
cytosine N3, thymine O4. For nucleotides the relationship between phosphate and
base binding is dependent on the type of metal ion. Eichhorn and Shin
3
studied the
effect of various metal ions on the melting temperature of DNA (Figure 1.1). The
authors suggest that magnesium ions increase
T
m
by binding to phosphate and
>
A, C
>
