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Antimicrobial Peptides pp 359–368Cite as

Using Disease-Associated Enzymes to Activate Antimicrobial Peptide Prodrugs

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1548))

Abstract

Prodrugs of antimicrobial peptides can be generated by modifying their sequences at their N-termini with a linker and a negatively charged promoiety. These modifications can be selectively reversed by a disease-associated enzyme, thereby confining the activity of the peptide to pathologically affected body parts. A general method for the generation of prodrug candidates, based on a linker constituting the substrate of a disease-associated protease and an oligo-glutamic acid promoiety, as well as a protocol to validate the activation of the prodrug, are described herein.

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Acknowledgements

This material is based upon works supported by the Science Foundation Ireland under Grants 05/RFP/CHE0063, 06/RFP/CHO024, 06/RFP/CHO024/EC07 and SFI 08/RFP/CHE1563, Enterprise Ireland under Grant PC/2005/164, RCSI under the RCSI Student Research Programme and the Higher Education Authority, Ireland under the BioAT programme in Cycle 5 of the Programme for Research in Third-Level Institutions.

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Authors and Affiliations

  1. Department of Pharmaceutical and Medicinal Chemistry, Centre for Synthesis and Chemical Biology, Royal College of Surgeons in Ireland, 123 Stephen’s Green, Dublin 2, Ireland

    Éanna B. Forde, Graeme Kelly, Hisham Makki, Zahraa Al-Sharshahi & Marc Devocelle

  2. Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Education and Research Centre, Dublin, Ireland

    Éanna B. Forde, Hisham Makki, Zahraa Al-Sharshahi & Deirdre Fitzgerald-Hughes

Authors
  1. Éanna B. Forde
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  2. Graeme Kelly
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  3. Hisham Makki
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  4. Zahraa Al-Sharshahi
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  5. Deirdre Fitzgerald-Hughes
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  6. Marc Devocelle
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Corresponding author

Correspondence to Marc Devocelle .

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Editors and Affiliations

  1. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Paul R. Hansen

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Forde, É.B., Kelly, G., Makki, H., Al-Sharshahi, Z., Fitzgerald-Hughes, D., Devocelle, M. (2017). Using Disease-Associated Enzymes to Activate Antimicrobial Peptide Prodrugs. In: Hansen, P. (eds) Antimicrobial Peptides. Methods in Molecular Biology, vol 1548. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6737-7_26

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  • DOI: https://doi.org/10.1007/978-1-4939-6737-7_26

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6735-3

  • Online ISBN: 978-1-4939-6737-7

  • eBook Packages: Springer Protocols

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