Novel compounds that interact with zinc finger proteins

Abstract

Compounds that interact with zinc finger proteins, or more generally, with chelated metal ions from a protein, present appreciable interest for the design of novel types of pharmacological agents, primarily based on the success of this approach for the development of antiviral (anti-HIV-1) agents. Such an approach has rarely been taken into account for developing agents effective against DNA viruses. Among them, human papillomaviruses (HPVs) produce debilitating disease, for which no effective cures are presently available. Institute of Molecular & Cell Biology discloses in this patent a series of polysulphides and dithiuram disulphides, that act as zinc chelators, subtracting in this way Zn(II) ions from some critical HPV proteins incorporating zinc fingers, such as the E6 oncoprotein. The compounds disclosed were synthesised by classical procedures and were assayed in vitro for their ability to induce zinc extrusion from the E6 protein of HPV-16, for their ability to inhibit the binding of E6 to E6AP and E6BP-glutathione-S-transferase (two coactivators of E6 mediated cellular transformation) and ex vivo for their effects on the viability of HPV infected cells. These compounds represent interesting leads for the development of novel types of antiviral/anticancer agents.

• antiviral agents
• dithiuram disulphides
• human papillomavirus
• oncoprotein
• polysulphides
• zinc chelators
• zinc finger proteins