Chemistry Reference
In-Depth Information
13
Artifi cial Restriction Agents:
Hydrolytic Agents for
DNA Cleavage
Fabrizio Mancin and Paolo Tecilla
13.1 Introduction
The inertness of DNA toward hydrolytic cleavage is tremendous. Indeed, the esti-
mated half-life times for a single P-O bond cleavage at 25 °C and pH 7 range from
hundreds of thousands to hundreds of millions of years.
1
Such hydrolytic resistance
contributes to the preservation of the genetic information, but also represents a
serious obstacle, since several biological processes involving DNA manipulation, e.g.
expression and duplication, repair of damages and elimination of foreign DNA,
require hydrolytic reactions. The solution of this problem is provided by a wealth
of hydrolytic enzymes, nucleases and topoisomerases, which effi ciently catalyse
DNA scission. Many such enzymes contain metal ions in their active sites, mainly
Ca(II), Mg(II) and Zn(II), that play a fundamental role in their catalytic action.
1b,2
As a matter of fact, the ability of metal ions to promote the hydrolytic cleavage
of esters has been well known by chemists for decades. However, the development
of synthetic agents capable to accelerate the hydrolysis of DNA has attracted sub-
stantial research efforts only in the last 20 years.
2a,3
There are several reasons that
justify the interest in such systems. First, the mechanistic information obtained in
the study of artifi cial agents could lead to a better understanding of the chemistry
of the corresponding hydrolytic enzymes. Second, they could be employed for
detoxifi cation of pesticides and chemical weapons, which often have phosphate
