Structure-based ligand design of novel bacterial RNA polymerase inhibitors.

ABSTRACT: Bacterial RNA polymerase (RNAP) is essential for transcription and is an antibacterial target for small molecule inhibitors. The binding region of myxopyronin B (MyxB), a bacterial RNAP inhibitor, offers the possibility of new inhibitor design. The molecular design program SPROUT has been used in conjunction with the X-ray cocrystal structure of Thermus thermophilus RNAP with MyxB to design novel inhibitors based on a substituted pyridyl-benzamide scaffold. A series of molecules, with molecular masses <350 Da, have been prepared using a simple synthetic approach. A number of these compounds inhibited Escherichia coli RNAP.

SUBMITTER: McPhillie MJ 

PROVIDER: S-EPMC4017976 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature