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Modulating the Antimicrobial Activity of Temporin L Through Introduction of Fluorinated Phenylalanine

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Abstract

Antimicrobial peptides (AMPs) are the promising future therapeutic candidates because of their multifunctional roles and unique mode of action against microbes. Despite several advantages, developing AMPs into therapeutic antibiotics is often associated with limitations, such as thermal and enzymatic stability, moderate antimicrobial activity and higher toxicity. We here report the synthesis of 2-fluoro- and 2,6-difluorophenyalanine, their introduction into naturally occurring antimicrobial peptide Temporin L (TL). We also report the antimicrobial and hemolytic activity of parent TL as well as the fluorinated variant in plasma and buffer conditions. Circular dichroism studies clearly show that fluorination reduces the helical propensity, thus accounting for lower activity. We further demonstrated that fluorinated TL can act as antimicrobial agents in creams and gels used for treating skin infections.

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Acknowledgments

C.S.S. and S.H thanks UGC for award of senior and junior research fellowship respectively. The authors gratefully acknowledge the SAIF Division of CSIR-CDRI for providing the spectroscopic data. Dr M.P. thank the Director, Central Drug Research Institute (CDRI), Lucknow, and SERB, DST India, for his encouragement and providing the seed money to establish the lab and carry out the work. This manuscript has CDRI Communication No.56/2015/WH.

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Authors and Affiliations

  1. Division of Medicinal and Process Chemistry, Central Drug Research Institute, B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India

    Subbaiah Chennam Setty & Wahajul Haq

  2. Division of Microbiology, Central Drug Research Institute, B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India

    Soyar Horam & Mukesh Pasupuleti

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  1. Subbaiah Chennam Setty
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  2. Soyar Horam
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  3. Mukesh Pasupuleti
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  4. Wahajul Haq
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Correspondence to Mukesh Pasupuleti or Wahajul Haq.

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Ethical Approval

This article does not contain studies with human or animal subjects. However, human blood was used in the hemolysis studies for which, Institutional human ethical committee, CSIR-CDRI, Lucknow, has approved the use of human blood for the experiments (CDRI/IEC/2014/A1). Written informed consent was obtained from the all the blood donor. For the pig skin experiment, the required skin was collected from the adult male animals, which were sacrificed for human consumption at local slaughter house. As the animals were not housed for the experimental purpose, no animal ethical permission was needed as per Indian animal ethics code.

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Setty, S.C., Horam, S., Pasupuleti, M. et al. Modulating the Antimicrobial Activity of Temporin L Through Introduction of Fluorinated Phenylalanine. Int J Pept Res Ther 23, 213–225 (2017). https://doi.org/10.1007/s10989-016-9553-5

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  • DOI: https://doi.org/10.1007/s10989-016-9553-5

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