A5022315111- Antimicrobial Peptides and Activities
- Antibiotic Resistance in Bacteria
- Microbial Natural Products and Biosynthesis
- Chemical Synthesis and Analysis
- Peptidase Inhibition and Analysis
- Biochemical and Structural Characterization
- Probiotics and Fermented Foods
- Cancer therapeutics and mechanisms
- Click Chemistry and Applications
- Antibiotic Use and Resistance
- Pneumonia and Respiratory Infections
- Carbohydrate Chemistry and Synthesis
Queen's University Belfast
2018-2024
University of Ulster
2019-2021
Belfast City Hospital
2019-2021
Queens University
2021
Brevicidine and laterocidine are two recently discovered lipopeptide antibiotics with promising antibacterial activity. Possessing a macrocyclic core, multiple positive charges, lipidated N-terminus, these lipopeptides exhibit potent selective activity against Gram-negative pathogens, including polymyxin-resistant isolates. Given the low amounts of brevicidine accessible by fermentation producing microorganisms, synthetic routes to present an attractive alternative. We here report convenient...
Brevicidine and laterocidine are macrocyclic lipodepsipeptides with selective activity against Gram-negative bacteria, including colistin-resistant strains. Previously, the core of these peptides was thought essential for antibacterial activity. In this study, we show that C-terminal amidation linear brevicidine scaffolds, substitution native Thr9, yields analogues retain potent low hemolysis parent compounds. Furthermore, an alanine scan both revealed aromatic basic amino acids within...
There remains a critical need for new antibiotics against multi-drug-resistant Gram-negative bacteria, major global threat that continues to impact mortality rates. Lipoprotein signal peptidase II is an essential enzyme in the lipoprotein biosynthetic pathway of making it attractive target antibacterial drug discovery. Although natural inhibitors LspA have been identified, such as cyclic depsipeptide globomycin, poor stability and production difficulties limit their use clinical setting. We...
Non-ribosomal peptides (NRPs) are a rich source of antibiotic candidates. However, it was recently discovered that resistance to NRPs can be mediated by d-stereoselective peptidases. The tridecaptins, class selectively target Gram-negative bacteria, degraded the d-peptidase TriF. Through analysis solution NMR structure tridecaptin A1, we have rationally synthesized new cyclic analogues retain strong antimicrobial activity and resistant
Antimicrobial peptides are a rich source of potential antibiotic candidates. The tridecaptins, family linear lipo-tridecapeptides, easily synthesized and show strong activity against Gram-negative bacteria. However, their composition includes several expensive amino acids, such as d/l diaminobutyric acid d-allo-isoleucine, significantly increasing cost synthesis. Herein, we report series new tridecaptin derivatives that much cheaper to synthesize retain multidrug-resistant
The brevicidine and laterocidine family of lipopeptide antibiotics exhibit strong activity against multidrug-resistant Gram-negative bacteria, while showing low propensity to induce resistance. Both peptides feature a branched lipid tail on the N-terminal residue, which for is chiral. Here, we report synthesis biological evaluation library analogues wherein replaced with linear achiral fatty acids. Optimal chain lengths were determined new colistin-resistant E. coli produced.
d-Stereoselective peptidases that degrade nonribosomal peptides (NRPs) were recently discovered and could have serious implications for the future of NRPs as antibiotics. Herein, we report chemical modifications can be used to impart resistance d-peptidases BogQ TriF. New tridecaptin A analogues synthesized retain strong antimicrobial activity significantly enhanced d-peptidase stability. In vitro assays confirmed synthetic ability bind their cellular receptor, peptidoglycan intermediate lipid II.
Brevicidine and laterocidine are two recently discovered lipopeptide antibiotics with promising antibacterial activity. Possessing a macrocyclic core, multiple positive charges, lipidated N -terminus, these lipopeptides exhibit potent selective activity against Gram-negative pathogens including polymyxin-resistant isolates. Given the low amounts of brevicidine accessible by fermentation producing microorganisms, synthetic routes to present an attractive alternative. We here report convenient...
Brevicidine and laterocidine are two recently discovered lipopeptide antibiotics with promising antibacterial activity. Possessing a macrocyclic core, multiple positive charges, lipidated <i>N</i>-terminus, these lipopeptides exhibit potent selective activity against Gram-negative pathogens including polymyxin-resistant isolates. Given the low amounts of brevicidine accessible by fermentation producing microorganisms, synthetic routes to present an attractive alternative. We here...
Brevicidine and laterocidine are two recently discovered lipopeptide antibiotics with promising antibacterial activity. Possessing a macrocyclic core, multiple positive charges, lipidated N-terminus, these lipopeptides exhibit potent selective activity against Gram-negative pathogens, including polymyxin-resistant isolates. Given the low amounts of brevicidine accessible by fermentation producing microorganisms, synthetic routes to present an attractive alternative. We here report convenient...