Chemistry Reference
In-Depth Information
Figure 13.12
Chemical structure of the Scrimin's ditopic Zn(II)-binding heptapeptide
An impressive high reactivity was recently reported by Yu and coworkers,
36a
who studied dimetallic Zn(II) complexes made by linking two cyclen ligands with
different spacers bearing alcoholic, phenolic or pyridinic moieties. The authors claim
complete nicking of plasmid DNA in only fi ve minutes at pH 7.1, 37 °C and 25 m M
complex concentration. Longer times of incubation result in further fragmentation
and DNA smearing on the electrophoresis gel. However, the complexes are active
only in the presence of vitamin C as reducing agent. Therefore, the occurrence of
some concurrent oxidative degradation pathway, involving the ligand backbone or
adventitious redox active metal ions, is possible. The same type of reactivity was also
observed in the case of the Zn(II) complexes of uracil-cyclen conjugate ligands.
36b
These results, although impressive if the mechanism proves to be really hydrolytic,
stress the importance of using caution when studying the mechanism of DNA cleav-
age, even when Zn(II) is employed as metal ion. Indeed this natural substrate is
really stable toward hydrolysis, but is also very delicate from other points of view
and competitive cleavage pathways are always possible.
13.5 Conjugation with DNA - affi ne Subunits
Simple considerations, supported by several examples reported in the case of oxida-
tive DNA cleaving agents,
37
suggest that the reactivity of hydrolytic systems should
be strongly enhanced when their structures comprise groups with high DNA affi nity.
Furthermore, such groups could also provide sequence specifi city to the cleaving
agents and thus open the way toward the obtainment of real artifi cial restriction
enzymes.
The obvious choice among the different families of compounds able to increase
DNA affi nity is the utilization of intercalators. Quite surprisingly, examples of metal
complexes appended to intercalating groups as hydrolytic agents are rare, and the
effects of such elements on the reactivity of the systems are not always straightfor-
ward. For example, in the case of the Scrimin's peptide discussed above,
35
the intro-
duction of an acridine moiety at the N-terminus of the heptapeptide resulted in a
slightly higher activity at low catalyst concentration compensated by a decrease at
higher concentrations.
