title: 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.
authors.affiliation: School of Chemistry and Faculty of Biological Sciences, University of Leeds , Leeds LS2 9JT, United Kingdom.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: McPhillie
authors.affiliation: School of Chemistry and Faculty of Biological Sciences, University of Leeds , Leeds LS2 9JT, United Kingdom.
authors.forename: Rachel
authors.initials: R
authors.lastname: Trowbridge
authors.affiliation: School of Chemistry and Faculty of Biological Sciences, University of Leeds , Leeds LS2 9JT, United Kingdom.
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Mariner
authors.affiliation: School of Chemistry and Faculty of Biological Sciences, University of Leeds , Leeds LS2 9JT, United Kingdom.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: O'Neill
authors.affiliation: School of Chemistry and Faculty of Biological Sciences, University of Leeds , Leeds LS2 9JT, United Kingdom.
authors.forename: A Peter
authors.initials: AP
authors.lastname: Johnson
authors.affiliation: School of Chemistry and Faculty of Biological Sciences, University of Leeds , Leeds LS2 9JT, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Chopra
authors.affiliation: School of Chemistry and Faculty of Biological Sciences, University of Leeds , Leeds LS2 9JT, United Kingdom.
authors.forename: Colin W G
authors.initials: CW
authors.lastname: Fishwick
keywords: Bacterial RNA polymerase; myxopyronin B; small molecule inhibitors; structure-based ligand discovery