Project Title

Peptide-Based Antibiotics to Inhibit Pathogenic and Clinically Relevant Bacteria Strains

Academic department under which the project should be listed

CSM - Chemistry and Biochemistry

Research Mentor Name

Mohammad A. Halim

Abstract (300 words maximum)

Multi-drug resistant bacteria pose a threat to humans as they are responsible for infectious diseases. The development of this resistance can be as a result of multiple mechanisms: efflux pump activation, which reduces bacteria intracellular antibiotic concentration, poor antibiotic affinity as a result of a protein that protects the target site, or mutations that alter DNA and topoisomerase gene coding which changes the residues in the binding sites so the antibiotic cannot effectively bind. Small molecule-based antibiotics often induce harmful off-target effects and lead to therapy resistance on prolonged use. Peptide-based antibiotics, in contrast, are highly target-specific and thus induce less toxic effect compared to small molecule antibiotics. In this study, we employed molecular docking, synthesis, characterization, and antibacterial assay of L27-11 peptide. This peptide was synthesized in a solid support of a rink amid resin using CEM Liberty Blue peptide synthesizer. The solid support and peptide complex was cleaved with a high percentage of TFA, filtered and precipitated with cold ether. Lyophilization of the peptide was achieved in a freeze-drying condition at -50 °C after adding of 10% acidic acid and subsequent freezing of the sample. Liquid chromatography results showed that the peptide was eluted at 1.42 mins. Three intense peaks associated with [M+2H]2+, [M+3H]3+, and [M+4H]4+ charge states are found at m/z 815.08, 543.83, and 408.17, respectively agreed with the theoretical charge states. Various concentrations of L27-11 peptide were tested for antibacterial activity using a Kirby-Bauer disk assay on several bacteria strains, including opportunistic human pathogen Pseudomonas aeruginosa 01, model Gram-positive and negative, Staphylococcus aureus and Escherichia coli, respectively and the clinically-relevant yeasts Candida albicans and auris. Initial assays demonstrate peptide susceptibility by P. aeruginosa and C. albicans. A broader microbial screen and determination of the minimal inhibitory concentration using a broth dilution assay is underway.

Disciplines

Bacteriology | Biochemistry | Medicinal-Pharmaceutical Chemistry | Organic Chemistry | Pathogenic Microbiology

This document is currently not available here.

COinS
 

Peptide-Based Antibiotics to Inhibit Pathogenic and Clinically Relevant Bacteria Strains

Multi-drug resistant bacteria pose a threat to humans as they are responsible for infectious diseases. The development of this resistance can be as a result of multiple mechanisms: efflux pump activation, which reduces bacteria intracellular antibiotic concentration, poor antibiotic affinity as a result of a protein that protects the target site, or mutations that alter DNA and topoisomerase gene coding which changes the residues in the binding sites so the antibiotic cannot effectively bind. Small molecule-based antibiotics often induce harmful off-target effects and lead to therapy resistance on prolonged use. Peptide-based antibiotics, in contrast, are highly target-specific and thus induce less toxic effect compared to small molecule antibiotics. In this study, we employed molecular docking, synthesis, characterization, and antibacterial assay of L27-11 peptide. This peptide was synthesized in a solid support of a rink amid resin using CEM Liberty Blue peptide synthesizer. The solid support and peptide complex was cleaved with a high percentage of TFA, filtered and precipitated with cold ether. Lyophilization of the peptide was achieved in a freeze-drying condition at -50 °C after adding of 10% acidic acid and subsequent freezing of the sample. Liquid chromatography results showed that the peptide was eluted at 1.42 mins. Three intense peaks associated with [M+2H]2+, [M+3H]3+, and [M+4H]4+ charge states are found at m/z 815.08, 543.83, and 408.17, respectively agreed with the theoretical charge states. Various concentrations of L27-11 peptide were tested for antibacterial activity using a Kirby-Bauer disk assay on several bacteria strains, including opportunistic human pathogen Pseudomonas aeruginosa 01, model Gram-positive and negative, Staphylococcus aureus and Escherichia coli, respectively and the clinically-relevant yeasts Candida albicans and auris. Initial assays demonstrate peptide susceptibility by P. aeruginosa and C. albicans. A broader microbial screen and determination of the minimal inhibitory concentration using a broth dilution assay is underway.