US 9,060,970 B2 · Bridge-helix cap: target and method for inhibition of bacterial RNA polymerase

Abstract

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.

Claims19

Dependent claims

A method for identifying an agent that binds to a bacterial ribonucleic acid polymerase (RNAP) bridge-helix cap target in a first entity, comprising the steps of:

(a) preparing a reaction solution including the agent to be tested and a first entity including a bacterial RNAP bridge-helix cap target, wherein the bacterial RNAP bridge-helix cap target comprises residues corresponding to, or alignable with, residues 561, 569, 665, 675, 677, and 680 of the β subunit or residues 690, 697, 758, and 763 of the β′ subunit of RNA polymerase from Escherichia coli;
and
(b) detecting at least one of the presence, extent, concentration-dependence, or kinetics of binding of the agent to the bridge-helix cap target, wherein the agent is not salinamide A.

Dependencies are inferred from the claim text.

Bridge-helix cap: target and method for inhibition of bacterial RNA polymerase

Life of this patent

Bridge-helix cap: target and method for inhibition of bacterial RNA polymerase

Life of this patent

Abstract

Claims19