Chemistry Reference
In-Depth Information
12
DNA Recognition and Binding by
Peptide - Metal Complex Conjugates
Alexandra Myari and Nick Hadjiliadis
12.1
Introduction
The design and synthesis of chemical agents capable of binding specifi cally to DNA
have gained great research interest in recent years.
1
The discovery of novel sequence
specifi cities, beyond the sequences recognized by the known natural restriction
endonucleases, may possibly offer extended possibilities in DNA manipulation.
2
Such specifi c DNA-binding agents could fi nd several applications in molecular
biology (sequencing, cloning) and clinical applications (gene regulation, gene therapy,
chemotherapy).
2
X - ray crystallography
3,4
has revealed many molecular details regarding protein-
DNA recognition. These involve the formation of a hydrogen-bonding network
between peptide donor groups (coming from the peptide backbone and amino acid
side chains) and the edges of the bases, consisting of what is called direct readout.
In addition, formation of specifi c complexes between the protein and DNA is often
followed by conformational changes of both protein and DNA molecules as well as
release of water molecules part of the DNA hydration spine.
3 - 5
Peptides are low molecular weight DNA-binding agents that can effectively
mimic the bulky proteins. Peptides have the same donor groups utilized by pro-
teins in the process of DNA recognition. They are also easily synthesized and their
amino-acid composition and chirality can be tuned in order to achieve the desired
DNA-binding properties. Binding of peptides has been thoroughly investigated and
