Abstract
Oncocin is a proline-rich antimicrobial peptide that inhibits protein synthesis by binding to the bacterial ribosome. In this work, the antimicrobial activity of oncocin was improved by systematic peptide mutagenesis and activity evaluation. We found that a pair of cationic substitutions (P4K and L7K/R) improves the activity by 2-4 fold (p < 0.05) against multiple Gram-negative bacteria. An in vitro transcription/translation assay indicated that the increased activity was not because of stronger ribosome binding. Rather a cellular internalization assay revealed a higher internalization rate for the optimized analogs thereby suggesting a mechanism to increase potency. In addition, we found that the optimized peptides' benefit is dependent upon nutrient-depleted media conditions. The molecular design and characterization strategies have broad potential for development of antimicrobial peptides.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 930-941 |
| Number of pages | 12 |
| Journal | Molecular Systems Design and Engineering |
| Volume | 3 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 2018 |
| Event | 2020 AIChE Annual Meeting - Virtual, Online Duration: Nov 16 2020 → Nov 20 2020 |
Bibliographical note
Funding Information:This work was supported by grants from the National Institutes of Health (R01GM121777 and R01GM111358) and by a grant from the National Science Foundation (CBET-1412283). We acknowledge computational support from the Minnesota Supercomputing Institute and from the Extreme Science and Engineering Discovery Environment, which is supported by National Science Foundation ACI-10535753.
Publisher Copyright:
© The Royal Society of Chemistry.