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Effect of hydrocarbon stapling on the properties of α-helical antimicrobial peptides isolated from the venom of hymenoptera

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Abstract

The impact of inserting hydrocarbon staples into short α-helical antimicrobial peptides lasioglossin III and melectin (antimicrobial peptides of wild bee venom) on their biological and biophysical properties has been examined. The stapling was achieved by ring-closing olefin metathesis, either between two S-2-(4′-pentenyl) alanine residues (S 5) incorporated at i and i + 4 positions or between R-2-(7′-octenyl) alanine (R 8) and S 5 incorporated at the i and i + 7 positions, respectively. We prepared several lasioglossin III and melectin analogs with a single staple inserted into different positions within the peptide chains as well as analogs with double staples. The stapled peptides exhibited a remarkable increase in hemolytic activity, while their antimicrobial activities decreased. Some single stapled peptides showed a higher resistance against proteolytic degradation than native ones, while the double stapled analogs were substantially more resistant. The CD spectra of the singly stapled peptides measured in water showed only a slightly better propensity to form α-helical structure when compared to native peptides, whereas the doubly stapled analogs exhibited dramatically enhanced α-helicity.

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Acknowledgments

This work was supported by the Czech Science Foundation, Grant No. 203/08/0536 and by Research Project No. Z40550506 of the Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic. We also thank Professor V.O. Kostroun, Cornell University, Ithaca, NY, for assistance with the preparation of this manuscript.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo 2, Prague 6, 16610, Czech Republic

    Hubert Chapuis, Jiřina Slaninová, Lucie Bednárová, Lenka Monincová, Miloš Buděšínský & Václav Čeřovský

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  1. Hubert Chapuis
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  2. Jiřina Slaninová
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  3. Lucie Bednárová
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  6. Václav Čeřovský
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Correspondence to Václav Čeřovský.

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Chapuis, H., Slaninová, J., Bednárová, L. et al. Effect of hydrocarbon stapling on the properties of α-helical antimicrobial peptides isolated from the venom of hymenoptera. Amino Acids 43, 2047–2058 (2012). https://doi.org/10.1007/s00726-012-1283-1

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  • DOI: https://doi.org/10.1007/s00726-012-1283-1

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