Affiliation: GlaxoSmithKline Research and Development
- A global approach to identify novel broad-spectrum antibacterial targets among proteins of unknown functionMagdalena Zalacain
Microbial, Musculoskeletal and Proliferative Diseases CEDD, Collegeville, PA 17426, USA
J Mol Microbiol Biotechnol 6:109-26. 2003..Moreover, this study demonstrates that different experimental procedures can produce apparently contradictory results...
- Peptide deformylase inhibitorsKelly Aubart
Microbial, Musculoskeletal, and Proliferative Diseases CEDD, GlaxoSmithKline Pharmaceuticals, Collegeville, PA 19426, USA
Prog Med Chem 44:109-43. 2006
- Phylogenomic and biochemical characterization of three Legionella pneumophila polypeptide deformylasesJianzhong Huang
Microbiology Department, GlaxoSmithKline, 1250 S Collegeville Road, Collegeville, PA 19426, USA
J Bacteriol 188:5249-57. 2006..pneumophila. These results indicate that even though L. pneumophila has three PDFs, they can be effectively inhibited by PDF inhibitors which can, therefore, have potent anti-L. pneumophila activity...
- Selection of retapamulin, a novel pleuromutilin for topical useStephen Rittenhouse
Department of Microbiology Research, MMPD CEDD, GlaxoSmithKline Pharmaceuticals, 1250 S Collegeville Rd, Collegeville, PA 19426 0989, USA
Antimicrob Agents Chemother 50:3882-5. 2006..12 microg/ml and 0.016 microg/ml, respectively. Retapamulin has a low propensity to select resistance and produces an in vitro postantibiotic effect...
- Characterization of Streptococcus pneumoniae TrmD, a tRNA methyltransferase essential for growthKaren O'Dwyer
Microbial, Musculoskeletal and Proliferative Diseases CEDD, GlaxoSmithKline, Collegeville, Pennsylvania 19426, USA
J Bacteriol 186:2346-54. 2004..Other heterologous nonsubstrate tRNA species, like, tRNA (Thr)(GGT), tRNA(Phe), and tRNA (Ala)(TGC), bind the enzyme with similar affinities, suggesting that tRNA specificity is achieved via a postbinding event(s)...
- Characterization of a novel fucose-regulated promoter (PfcsK) suitable for gene essentiality and antibacterial mode-of-action studies in Streptococcus pneumoniaePan F Chan
Microbial, Musculoskeletal and Proliferative Diseases Center of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, Collegeville, Pennsylvania 19426, USA
J Bacteriol 185:2051-8. 2003..The endogenous fuculose kinase promoter is a tightly regulated, titratable promoter which will be useful for target validation and for confirmation of the mode of action of novel antibacterial drugs in S. pneumoniae...
- Understanding the origins of time-dependent inhibition by polypeptide deformylase inhibitorsRachel Totoritis
Department of Biological Reagents, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA
Biochemistry 50:6642-54. 2011..Both of these interactions between the inhibitor and enzyme were found to be necessary to observe time-dependent inhibition, as elimination of either leads to its loss...
- Mechanism of time-dependent inhibition of polypeptide deformylase by actinoninGlenn S Van Aller
Enzymology and Mechanistic Pharmacology, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA
Biochemistry 44:253-60. 2005..T., et al. (2004) Bioorg. Chem. 32, 178-191]. This study substantially extends our understanding of PDF inhibition and may facilitate the development of novel antibiotics...
- A rapid microtiter plate assay for measuring the effect of compounds on Staphylococcus aureus membrane potentialDaniel R Gentry
Antibacterial Discovery Performance Unit, Infectious Diseases Center of Excellence in Drug Discovery, GlaxoSmithKline Pharmaceuticals, Collegeville, PA 19426, United States
J Microbiol Methods 83:254-6. 2010..In a screen of 372 compounds from a synthetic compound collection with anti-Escherichia coli activity due to unknown modes of action at least 17% demonstrated potent membrane activity, enabling rapid discrimination of nuisance compounds...
- Staphylococcus aureus formyl-methionyl transferase mutants demonstrate reduced virulence factor production and pathogenicityThomas Lewandowski
Antibacterial Discovery Performance Unit, Infectious Diseases Therapeutic Area, GlaxoSmithKline, Collegeville, Pennsylvania, USA
Antimicrob Agents Chemother 57:2929-36. 2013....
- Inhibitors of pantothenate kinase: novel antibiotics for staphylococcal infectionsAnthony E Choudhry
Microbial, Musculoskeletal and Proliferative Diseases and Bioinformatics, GlaxoSmithKline Pharmaceuticals, Collegeville Pennsylvania 19426, USA
Antimicrob Agents Chemother 47:2051-5. 2003..Here we report the identification of the Staphylococcus aureus coaA gene and characterization of the enzyme. We have also identified a series of low-molecular-weight compounds which are effective inhibitors of S. aureus CoaA...
- Comparative analysis of the antibacterial activity of a novel peptide deformylase inhibitor, GSK1322322Karen O'Dwyer
Antibacterial Discovery Performance Unit, Infectious Disease Therapeutic Area, GlaxoSmithKline, Collegeville, Pennsylvania, USA
Antimicrob Agents Chemother 57:2333-42. 2013..Given the antibacterial potency demonstrated against this panel of organisms, GSK1322322 represents a valuable alternative therapy for the treatment of infectious diseases caused by drug-resistant pathogens...
- Novel antibacterials: a genomics approach to drug discoveryPan F Chan
Department of Microbiology Microbial, Musculoskeletal and Proliferative Diseases CEDD, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426 0989, USA
Curr Drug Targets Infect Disord 2:291-308. 2002..Genomics can also increase the chemical diversity against which the novel targets can be screened...
- Insights into catalysis by a knotted TrmD tRNA methyltransferasePatricia A Elkins
GlaxoSmithKline, 709 Swedeland Road, UE0447, King of Prussia, PA 19406, USA
J Mol Biol 333:931-49. 2003..Mutational analyses demonstrate that the knot is important for AdoMet binding and catalytic activity, and that the C-terminal domain is not only required for tRNA binding but plays a functional role in catalytic activity...