Here, we report the design, synthesis, and evaluation of a series of inhibitors of Staphylococcus aureus BPL (SaBPL), where the central acyl phosphate of the natural intermediate biotinyl-5'-AMP (1) is replaced by a sulfonamide isostere. Acylsulfamide (6) and amino sulfonylurea (7) showed potent in vitro inhibitory activity (Ki = 0.007 ± 0.003 and 0.065 ± 0.03 μM, respectively) and antibacterial activity against S. aureus ATCC49775 with minimum inhibitory concentrations of 0.25 and 4 μg/mL, respectively. Additionally, the bimolecular interactions between the BPL and inhibitors 6 and 7 were defined by X-ray crystallography and molecular dynamics simulations. The high acidity of the sulfonamide linkers of 6 and 7 likely contributes to the enh...
Sulfonamides represent the oldest synthetic antibacterial agents; however, their central position in...
Biotin protein ligase (BPL) is an enzyme found in all organisms, and is required for the attachment ...
Biotin protein ligase (BPL) inhibitors are a novel class of antibacterial that target clinically imp...
Replacing the labile adenosinyl-substituted phosphoanhydride of biotinyl-5'-AMP with a N1-benzyl sub...
There is a desperate need to develop new antibiotic agents to combat the rise of drug-resistant bact...
There is a desperate need for novel antibiotic classes to combat the rise of drug resistant pathogen...
There is a well-documented need to replenish the antibiotic pipeline with new products to combat the...
There is a desperate need for novel antibiotic classes to combat the rise of drug resistant pathogen...
There is a well documented need to replenish the antibiotic pipeline with new agents to combat the r...
Replacing the labile adenosinyl-substituted phosphoanhydride of biotinyl-5′-AMP with a N1-benzyl sub...
Antibiotics are defined as chemical substances that inhibit or limit the growth of microorganisms. S...
Biotin protein ligase (BPL) inhibitors are a novel class of antibacterial that target clinically imp...
Biotin protein ligase (BPL) is a ubiquitous enzyme that catalyzes the conjugation of biotin and ATP ...
This thesis reports the development of selective and potent small molecule inhibitors of Staphylococ...
Inhibitors of Staphylococcus aureus biotin protein ligase (SaBPL) are generated by replacing the acy...
Sulfonamides represent the oldest synthetic antibacterial agents; however, their central position in...
Biotin protein ligase (BPL) is an enzyme found in all organisms, and is required for the attachment ...
Biotin protein ligase (BPL) inhibitors are a novel class of antibacterial that target clinically imp...
Replacing the labile adenosinyl-substituted phosphoanhydride of biotinyl-5'-AMP with a N1-benzyl sub...
There is a desperate need to develop new antibiotic agents to combat the rise of drug-resistant bact...
There is a desperate need for novel antibiotic classes to combat the rise of drug resistant pathogen...
There is a well-documented need to replenish the antibiotic pipeline with new products to combat the...
There is a desperate need for novel antibiotic classes to combat the rise of drug resistant pathogen...
There is a well documented need to replenish the antibiotic pipeline with new agents to combat the r...
Replacing the labile adenosinyl-substituted phosphoanhydride of biotinyl-5′-AMP with a N1-benzyl sub...
Antibiotics are defined as chemical substances that inhibit or limit the growth of microorganisms. S...
Biotin protein ligase (BPL) inhibitors are a novel class of antibacterial that target clinically imp...
Biotin protein ligase (BPL) is a ubiquitous enzyme that catalyzes the conjugation of biotin and ATP ...
This thesis reports the development of selective and potent small molecule inhibitors of Staphylococ...
Inhibitors of Staphylococcus aureus biotin protein ligase (SaBPL) are generated by replacing the acy...
Sulfonamides represent the oldest synthetic antibacterial agents; however, their central position in...
Biotin protein ligase (BPL) is an enzyme found in all organisms, and is required for the attachment ...
Biotin protein ligase (BPL) inhibitors are a novel class of antibacterial that target clinically imp...