Synthesis and Characterization of Antimicrobial Peptides Targeting the DNA Gyrase of Mycobacterium Tuberculosis
Disciplines
Bacteriology | Biochemistry | Medicinal-Pharmaceutical Chemistry
Abstract (300 words maximum)
Mycobacterium tuberculosis is a microorganism that causes the disease tuberculosis. The mycobacterium tuberculosis vaccine was developed over a century ago and is widely available. Despite this, tuberculosis is the cause of around two million deaths each year, with most of these deaths occurring in undeveloped and developing countries. New production of fast-acting, cost-effective treatments to tuberculosis are crucial in allaying global suffering. Antimicrobial peptides have shown promise in treating bacterial infections due to their high specificity, relatively low cost, and use against a wide range of microorganisms. DNA Gyrase is a topoisomerase necessary for replication in bacteria and is the target of many antibiotics. Antimicrobial peptides have been shown to instead induce cell death in bacteria via electrostatic interactions between the negatively charged bacterial cell wall and the positively charged peptide. Three antimicrobial peptides (Temporin L, Temporin A, and SMAP-29) were modelled using Alpha fold and tested their binding affinity to DNA Gyrase through docking via HDOCK. Temporin L was found to have the most negative docking score, followed by SMAP-29 and Temporin A respectively. These peptides were synthesized using a Liberty Blue Microwave Peptide Synthesizer. Each peptide product was dried, cleaved, and isolated for further studies. Observed mass spectrometry data for each peptide was found to closely resemble theoretical data in terms of m/z. Visible peaks were found at the [M+H]+ and [M+2H]2+ ions for Temporin L, the [M+H]+, [M+2H]2+, and [M+3H]3+ ions for Temporin A, and the [M+H]3+ through [M+7H]7+ ions for SMAP-29. Further testing will be performed to assess the inhibitory effects of these three antimicrobial peptides against the Mycobacterium tuberculosis.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad A. Halim
Synthesis and Characterization of Antimicrobial Peptides Targeting the DNA Gyrase of Mycobacterium Tuberculosis
Mycobacterium tuberculosis is a microorganism that causes the disease tuberculosis. The mycobacterium tuberculosis vaccine was developed over a century ago and is widely available. Despite this, tuberculosis is the cause of around two million deaths each year, with most of these deaths occurring in undeveloped and developing countries. New production of fast-acting, cost-effective treatments to tuberculosis are crucial in allaying global suffering. Antimicrobial peptides have shown promise in treating bacterial infections due to their high specificity, relatively low cost, and use against a wide range of microorganisms. DNA Gyrase is a topoisomerase necessary for replication in bacteria and is the target of many antibiotics. Antimicrobial peptides have been shown to instead induce cell death in bacteria via electrostatic interactions between the negatively charged bacterial cell wall and the positively charged peptide. Three antimicrobial peptides (Temporin L, Temporin A, and SMAP-29) were modelled using Alpha fold and tested their binding affinity to DNA Gyrase through docking via HDOCK. Temporin L was found to have the most negative docking score, followed by SMAP-29 and Temporin A respectively. These peptides were synthesized using a Liberty Blue Microwave Peptide Synthesizer. Each peptide product was dried, cleaved, and isolated for further studies. Observed mass spectrometry data for each peptide was found to closely resemble theoretical data in terms of m/z. Visible peaks were found at the [M+H]+ and [M+2H]2+ ions for Temporin L, the [M+H]+, [M+2H]2+, and [M+3H]3+ ions for Temporin A, and the [M+H]3+ through [M+7H]7+ ions for SMAP-29. Further testing will be performed to assess the inhibitory effects of these three antimicrobial peptides against the Mycobacterium tuberculosis.