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Tetrahydropiperic acid (THPA) conjugated cationic hybrid dipeptides as antimicrobial agents

The Journal of Antibiotics volume 74, pages 480–483 (2021)Cite this article

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Abstract

The present work describes the synthesis of hybrid dipeptides H-Lys-Gpn-PEA, C1; H-Lys-β3,3AC6C-PEA, C2, and THPA conjugated dipeptides, THPA-Lys-Gpn-PEA, C3, and THPA-Lys-β3,3AC6C-PEA, C4. All the peptides were evaluated against both Gram-negative and Gram-positive bacterial strains. Among all, peptide C4 exhibited the most potent activity with MIC 1.56 μM against P. aeruginosa (MTCC 424) and S. aureus (MTCC 737). Further, time-kill kinetics, fluorescence assays, and scanning electron microscopy (SEM) studies were performed in order to understand the mechanism of action and efficacy of peptide C4, The fluorescence assays and SEM images demonstrated the bacterial killing through membrane disruption. The peptide C4 exhibited very low hemolytic activity with negligible cytotoxicity against normal human breast cell line FR2.

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Acknowledgements

We acknowledge the Council of Scientific and Industrial Research (CSIR), New Delhi, for financial assistance. JuR is thankful to UGC for Senior Research Fellowship (SRF). GS is thankful to ICMR for Senior Research Fellowship (SRF).

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Author notes

  1. These authors contributed equally: Junaid ur Rahim, Gurpreet Singh

Authors and Affiliations

  1. Medicinal Chemistry Division, Council of Scientific & Industrial Research-Indian Institute of Integrative Medicine(CSIR-IIIM), Jammu-180001, India

    Junaid ur Rahim, Sudha Shankar & Rajkishor Rai

  2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India

    Junaid ur Rahim, Gurpreet Singh, Sudha Shankar, Meenu Katoch & Rajkishor Rai

  3. Microbial Biotechnology Division, Council of Scientific & Industrial Research-Indian Institute of Integrative Medicine(CSIR-IIIM), Jammu-180001, India

    Gurpreet Singh & Meenu Katoch

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  1. Junaid ur Rahim
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  3. Sudha Shankar
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  4. Meenu Katoch
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  5. Rajkishor Rai
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Correspondence to Meenu Katoch or Rajkishor Rai.

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ur Rahim, J., Singh, G., Shankar, S. et al. Tetrahydropiperic acid (THPA) conjugated cationic hybrid dipeptides as antimicrobial agents. J Antibiot 74, 480–483 (2021). https://doi.org/10.1038/s41429-021-00419-0

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