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Synthesis and biological evaluation of nectriatide derivatives, potentiators of amphotericin B activity

The Journal of Antibiotics volume 77, pages 214–220 (2024)Cite this article

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Abstract

Nectriatide 1a, a naturally occurring cyclic tetrapeptide, has been reported to a potentiator of amphotericin B (AmB) activity. In order to elucidate its structure-activity relationships, we synthesized nectriatide derivatives with different amino acids in solution-phase synthesis and evaluated AmB-potentiating activity against Candida albicans. Among them, C-and N-terminal protected linear peptides were found to show the most potent AmB-potentiating activity.

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Acknowledgements

This study was supported by JSPS KAKENHI Grant Number JP19K05719 (KN), JP22K05333 (KN) and JP21K15284 (KK), The Tokyo Biochemical Research Foundation (now Chugai Foundation for Innovative Drug Discovery Science: C-FINDs) (KK), The Research Foundation for Pharmaceutical Sciences (KK) and Kitasato University Research Grant for Young Researchers (KK).

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Authors and Affiliations

  1. Microbial Chemistry and Medical Research Laboratories, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Kenichiro Nagai, Keisuke Kobayashi, Ryosuke Miyake, Yukino Sato, Reiko Seki, Taichi Ohshiro & Hiroshi Tomoda

  2. Department of Fisheries, Faculty of Agriculture and Agricultural Technology and Innovation Research Institute, Kindai University, 3327-204 Nakamachi, Nara, 631-8505, Japan

    Takashi Fukuda

  3. Division of Natural Product Chemistry, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi, 981-8558, Japan

    Akiho Yagi & Ryuji Uchida

Authors
  1. Kenichiro Nagai
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  2. Keisuke Kobayashi
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  3. Ryosuke Miyake
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  4. Yukino Sato
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  5. Reiko Seki
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  6. Takashi Fukuda
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  7. Akiho Yagi
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  8. Ryuji Uchida
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  9. Taichi Ohshiro
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  10. Hiroshi Tomoda
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Correspondence to Kenichiro Nagai.

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Nagai, K., Kobayashi, K., Miyake, R. et al. Synthesis and biological evaluation of nectriatide derivatives, potentiators of amphotericin B activity. J Antibiot 77, 214–220 (2024). https://doi.org/10.1038/s41429-023-00700-4

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