Researchers claim to have got closer to understanding how the platinum-based drug cisplatin acts to fight cancer, it has been reported.

Prior to the research, understanding of the drug's molecular interactions with the enzymes it aims to interrupt has been scant.

However, two new papers from the University of Munich claim to show the first crystal structures of cisplatin complexed with two key enzymes, with the crystal structure indicating how a rogue DNA polymerase replicates over cisplatin adducts, chemicalandengineeringnews.com reports

One paper from Thomas Carrell and Karl-Peter Hopfner details the structure of a renegade DNA Polymerase called Pol h, which it is claimed manages to replicate over unwelcome DNA adducts, and in so doing is not stalled by cisplatin.

According to their findings, Pol h is able to do this by having a much looser grip on DNA than other polymerases, thus permitting the adducts to fit into the catalytic sites.

It is hoped that through understanding how a tumour's DNA replication machinery beats cisplatin adducts, new derivatives of the drug can be formulated to more effectively attack tumours.

A further paper from Professor Carell and Patrick Cramer claims to show that the transcription is blocked by cisplatin adducts cannot attach themselves into the RNA polymerase catalytic site.

Source:

Discerning how an anticancer drug meddles with replication, transcription, 12/11/07
http://pubs.acs.org/cen/news/85/i46/8546notw4.html

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