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Chemical Biology

A supplement providing a snapshot of the latest developments in chemical biology



Battle of the bulge


25 October 2006

Helical molecules that bind to bulges in RNA could lead to anti-HIV drugs, according to research from the US. 

Nucleic acids such as DNA and RNA normally exist in a duplex structure, where two strands are joined as bases from each strand pair up. Where the bases remain unpaired a bulge is formed and these often have biological functions. For example, bulges in RNA from HIV are known to be involved in controlling the virus's replication. Now, Irving Goldberg and his team from Harvard Medical School and Northeastern University, Boston, have designed a small molecule that can bind specifically to these bulges in HIV RNA. 

HIV virus

HIV virus

"This is the first report of a designed molecule binding specifically with bulged RNA"
Goldberg's RNA binders have a helical structure, which the group based on the structure of a naturally occurring antibiotic, neocarzinostatin. They have shown that this antibiotic binds to and cleaves DNA bulges, but shows poor binding to RNA. However, the new molecules lack some of the antibiotic's organic groups, enabling a better fit with the RNA bulge. 'This is the first report of a designed molecule binding specifically with bulged RNA,' said Goldberg. 

Goldberg said that the team hopes to use these compounds as templates for molecules that will inactivate the viral RNA. But, for drug development, a good understanding of the specificity for particular nucleic acid sequences will be needed, he added. 

It is important to understand how small molecules interact with RNA, agreed Christine Chow, an expert in nucleic acid interactions from Wayne State University, in the US. 'This is a fresh example in which refining known DNA binders to give enhanced selectivity for RNA targets can produce leads for antiviral drug development,' she said. 

Katherine Vickers 

References

Z Xiao, N Zhang, Y Lin, GB Jones and IH Goldberg, Chem Commun, 2006, 4431-4433,
DOI: 10.1039/B610007d