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Pharmaceuticals

Fighting HIV With Multivalent Gold Nanoparticles

May 19, 2008 | A version of this story appeared in Volume 86, Issue 20

A therapeutically inactive small molecule has been transformed into a potent drug for fighting HIV simply by conjugating the compound to a gold nanoparticle (J. Am. Chem. Soc., DOI: 10.1021/ja710321g). A team led by Daniel L. Feldheim of the University of Colorado, Boulder; David M. Margolis of the University of North Carolina, Chapel Hill; and Christian Melander of North Carolina State University developed the strategy in which several copies of a compound that binds only weakly to a target are attached to a nanoparticle to create a multivalent agent that binds strongly. These nanoparticle-small-molecule conjugates, which are the size of proteins, provide multiple contact points for a biological receptor, thereby creating a strong interaction. The receptor in this case is CCR5, which HIV hijacks to gain entry to a cell. The researchers took SDC-1721, a compound that binds only weakly to CCR5, and attached 12 copies of the molecule to a 2-nm gold particle. On their own neither SDC-1721 nor the gold nanoparticles are able to keep HIV from infecting cells, but the SDC-1721-nanoparticle conjugate inhibits HIV replication at a concentration of just 10 nM.

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