Rutgers, the State University of New Jersey

David Degen

Richard H Ebright

Yon W Ebright

Yu Feng

Yu Zhang

Katherine Y Ebright

The invention provides bipartite inhibitors of bacterial RNA polymerase having the general structural formula (I):X-&#x3b1;-Y&#x2003;&#x2003;(I)wherein X is an moiety that binds to the rifamycin binding site of a bacterial RNA polymerase, Y is a moiety that binds to the GE23077 binding site of a bacterial RNA polymerase, and &#x3b1; is a linker. The invention also provides compositions comprising such compounds, methods of making such compounds, and methods of using said compounds. The invention has applications in control of bacterial gene expression, control of bacterial growth, antibacterial chemistry, and antibacterial therapy.

Bipartite inhibitors of bacterial RNA polymerase

The invention provides compounds of formula (I): and salts thereof, wherein X and Y have any of the values defined herein. The compounds inhibit bacterial RNA polymerase, inhibit bacterial growth, and have applications in, analysis of RNA polymerase structure and function, control of bacterial gene expression, control of bacterial growth, antibacterial chemistry, antibacterial therapy, and drug discovery.

Antibacterial agents: salinamide derivatives

The invention provides bipartite inhibitors of bacterial RNA polymerase having the general structural formula (I): X-&#x3b1;-Y (I) wherein X is an moiety that binds to the rifamycin binding site of a bacterial RNA polymerase, Y is a moiety that binds to the GE23077 binding site of a bacterial RNA polymerase, and is a linker. The invention also provides compositions comprising such compounds, methods of making such compounds, and methods of using said compounds. The invention has applications in control of bacterial gene expression, control of bacterial growth, antibacterial chemistry, and antibacterial therapy.

It has been discovered that the Sal target represents a new and promising target for antibacterial drug discovery. The Sal target is distinct from the rifamycin target and from the CBR703 target. This indicates that antibacterial compounds that function through the Sal target should exhibit no, or minimal, cross-resistance with rifamycins and CBR703. This further implies that it should be possible to co-administer antibacterial compounds that function through the Sal target together with a rifamycin, together with CBR703, or together with both a rifamycin and CBR703, in order to achieve additive or synergistic antibacterial effects and in order to suppress or eliminate the emergence of resistance.

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New Brunswick, NJ, United States of America

David Degen