Small Platinum Drugs Inhibit HIV Replication

Researchers have used small platinum-containing molecules to inhibit an HIV zinc finger protein, which prevents the HIV virus from replicating. Additional research is expected to show that these molecules will also inhibit zinc finger proteins in cancer cells.

A zinc finger is a protein domain that can bind to DNA. A zinc finger consists of two anti-parallel beta strands and an alpha helix. One very-well-explored sub-set of zinc-fingers (the C2H2 class) comprises a pair of cysteine residues in the beta sheets and two histidine residues in the alpha helix which are responsible for binding a zinc ion.

The structure of each individual finger is highly conserved and consists of about 30 amino acid residues, constructed as a beta-beta-alpha fold and held together by the zinc ion. The alpha helix occurs at the C-terminal part of the finger, while the beta-sheet occurs at the N-terminal part.

Many transcription factors, regulatory proteins, and other proteins that interact with DNA contain zinc fingers. These proteins typically interact with the major groove along the double helix of DNA in which case the zinc fingers are arranged around the DNA strand in such a way that the alpha-helix of each finger contacts the DNA, forming an almost continuous stretch of alpha-helices around the DNA molecule.

Investigators at Virginia Commonwealth University (Richmond, USA) studied the C-terminal finger of the HIV NCp7 protein. They reported in the May 30, 2006, issue of Chemistry & Biology that interacting with platinum resulted in ejection of the zinc ion from the peptide accompanied by loss of tertiary structure and protein activity.

"When we target specific viruses with drugs, over time patients can become resistant to treatment and the drug becomes ineffective. Therefore, novel biological processes and proteins are attractive targets for antiviral drug development,” said senior author Dr. Nicholas Farrell, professor of chemistry at Virginia Commonwealth University.



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