Research Seminar Series: Dr. Rakesh Kumar Tiwari - "Design, Synthesis, and Evaluation of Amphipathic Cyclic Peptides for the Treatment of Resistant Pathogenic Bacteria" - Keck Graduate Institute January 22, 2021, 12:00 pm Skip to main content
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rakesh tiwari

Please join us for Dr. Rakesh Kumar Tiwari, Assistant Professor of Biopharmaceutical and Biomedical Sciences, Chapman University  

The increasing number of multi-drug resistant pathogens created a global issue of antimicrobial-resistant due to the overuse of antibiotics. As a result, the discovery of newer classes of drugs is vital to alleviate infectious diseases caused by resistant microbial strains.  Antibacterial peptides are an emerging class of antibacterial agents against multidrug-resistant pathogenic bacteria. Previously, cyclic peptide [R4W4] containing positively-charged arginine (R) and hydrophobic tryptophan (W) residues had antibacterial activity with a minimum inhibitory concentration (MIC) value of 4 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA) and 42 µg/mL against Pseudomonas aeruginosa (PSA). We selected cyclic peptide [R4W4] as a lead compound for the development of effective broad-spectrum antimicrobial agents. Structure activity-relationships (SAR) were performed to optimize the antibacterial activity of the cyclic peptide by modification in the amino acid residues, increasing the number of residues, conjugation with classical antibiotics (levofloxacin), and with fatty acylation. Furthermore, newer series of peptides were synthesized by utilizing unnatural hydrophobic amino acids. A combination of selected lead peptides with commonly used antibiotics demonstrated effectiveness against Gram+ve and Gram-ve pathogen. The antimicrobial activities were evaluated using microbroth assay to determine MICs of synthesized compounds against MRSA, Klebsiella pneumoniae carbapenemase-producing strains (KPC), Pseudomonas aeruginosa (PSA), and Escherichia coli using meropenem and vancomycin as positive controls. The stability and cytotoxicity of synthesized peptides were evaluated against human serum, human red blood cells, and normal cell lines. This presentation will provide an overview of optimized antimicrobial peptides, which could be used as potent antimicrobial agents against resistant pathogens.

Date/Time: Friday, January 22, 12:00 – 1:00 p.m.

Location: Via Zoom

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PhD in Applied Life Sciences Program
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(909) 607-0120
Email:
kathryn_mcnevin@kgi.edu
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