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Improved antimicrobial peptides based on acyl-lysine oligomers

Nature Biotechnology volume 25, pages 657–659 (2007)Cite this article

Abstract

We describe peptidomimetic oligomers that show rapid, nonhemolytic, broad-spectrum bactericidal properties in mice and do not induce the emergence of resistance. The oligomers contain acyl chains, which prevent the formation of stable secondary structure. This design appears advantageous over conventional antimicrobial peptides with respect to in vivo efficacy and safety, and may provide a convenient platform for the development of peptide antibiotics.

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Figure 1: OAK library design and in vitro properties of C12K-7α8.
Figure 2: In vivo studies.

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Acknowledgements

This work was supported by The Israel Science Foundation (grant no. 387/03) and by BiolineRx (grant no. 2006992).

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Authors and Affiliations

  1. Department of Biotechnology & Food Engineering, Technion-Israel Institute of Technology, Haifa, 32000, Israel

    Inna S Radzishevsky, Shahar Rotem, Dmitry Bourdetsky & Amram Mor

  2. Division of Epidemiology, Tel Aviv Sourasky Medical Center, Tel Aviv, 64239, Israel

    Shiri Navon-Venezia & Yehuda Carmeli

Authors
  1. Inna S Radzishevsky
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  2. Shahar Rotem
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  3. Dmitry Bourdetsky
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  4. Shiri Navon-Venezia
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  5. Yehuda Carmeli
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  6. Amram Mor
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Contributions

I.S.R. synthesized reagents, performed research, analyzed data, wrote the paper; S.R. performed research (SPR and LC/MS experiments), analyzed data; D.B. performed research (in vivo blood concentrations), analyzed data; S.N.-V. performed research (in vivo toxicity and efficacy experiments), analyzed data; Y.C. designed research (in vivo toxicity and efficacy experiments), analyzed data; A.M. conceived the idea of peptide-mimetic AK oligomers, designed the OAK library, analyzed data, wrote the paper. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Amram Mor.

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Competing interests

This research was partly sponsored by BiolineRX, a drug development company supported by grants from the Israel Ministry of Trade and Industry, Chief Scientist's Office

Supplementary information

Supplementary Fig. 1

Dose-dependent binding kinetics of C12K-7α8 and MSI-78 as determined by SPR. (PDF 85 kb)

Supplementary Fig. 2

Secondary structures assessment. (PDF 83 kb)

Supplementary Fig. 3

Bacterial dissemination in-vivo. (PDF 59 kb)

Supplementary Fig. 4

Quantification of peptide concentrations in blood after i.p. administration. (PDF 43 kb)

Supplementary Fig. 5

Acute toxicity of C12K-7α8. (PDF 79 kb)

Supplementary Table 1

Physical and cytotoxic properties of representative OAKs. (PDF 14 kb)

Supplementary Table 2

Activity of C12K-7α8 against a panel of Gram-negative bacteria. (PDF 27 kb)

Supplementary Table 3

Binding properties of C12K-7α8 and MSI-78 as determined by SPR. (PDF 72 kb)

Supplementary Methods (PDF 124 kb)

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Radzishevsky, I., Rotem, S., Bourdetsky, D. et al. Improved antimicrobial peptides based on acyl-lysine oligomers. Nat Biotechnol 25, 657–659 (2007). https://doi.org/10.1038/nbt1309

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