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Updated: May 10, 2026

Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
Published on: May 4, 2018
Systematic study of non-natural short cationic lipopeptides as novel broad-spectrum antimicrobial agents
Sandeep Lohan1, Swaranjit S Cameotra, Gopal S Bisht
1Department of Pharmacy, Jaypee University of Information Technology, Solan, 173234, India.
Abstract:
We describe the design and synthesis of a new series of non-natural short cationic lipopeptides (MW = 700) as antimicrobial agents. All of the synthesized lipopeptides were tested against a range of microbes such as Gram-positive, Gram-negative bacteria, fungi including methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). By systematic study of design template, we found that three ornithine residues conjugated with myristic acid are minimum requirement for a compound to be an antimicrobial agent. The most potent lipopeptide LP16 possesses broad-spectrum antimicrobial activity and has MICs in the range of 1.5-6.25 μg/mL against Escherichia coli, S. aureus, Pseudomonas aeruginosa, Bacillus subtilis, and MRSE. All lipopeptides showed high selectivity toward microbial strains as compared to human red blood cells (HC50 > 250 μg/mL). Moreover, most potent lipopeptides (LP16 and LP23) did not induce drug resistance in S. aureus even after 15 rounds of passaging. In addition, a representative lipopeptide (LP16) showed tryptic stability for 24 h. These results suggest the potential of short cationic lipopeptides to boost the discovery of future antimicrobial therapeutics.
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