Journal of the Korean Magnetic Resonance Society (한국자기공명학회논문지)

Korean Magnetic Resonance Society (한국자기공명학회)
권호 표지
DOI QR코드

DOI QR Code

Structure-Activity Relationship of the N-terminal Helix Analog of Papiliocin, PapN

  • Jeon, Dasom (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Jeong, Min-Cheol (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Kim, Jin-Kyoung (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Jeong, Ki-Woong (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Ko, Yoon-Joo (National Center for Inter-University Research Facilities, Seoul National University) ;
  • Kim, Yangmee (Department of Bioscience and Biotechnology, Konkuk University)
  • Received : 2015.08.10
  • Accepted : 2015.09.25
  • Published : 2015.10.10
Download PDF
⟨ Previous Next ⟩

Abstract

Papiliocin, from the swallowtail butterfly, Papilio xuthus, shows high bacterial cell selectivity against Gram-negative bacteria. Recently, we designed a 22mer analog with N-terminal helix from $Lys^3$ to $Ala^{22}$, PapN. It shows outstanding antimicrobial activity against Gram-negative bacteria with low toxicity against mammalian cells. In this study, we determined the 3-D structure of PapN in 300 mM DPC micelle using NMR spectroscopy and investigated the interactions between PapN and DPC micelles. The results showed that PapN has an amphipathic ${\alpha}$-helical structure from $Lys^3$ to $Lys^{21}$. STD-NMR and DOSY experiment showed that this helix is important in binding to the bacterial cell membrane. Furthermore, we tested antibacterial activities of PapN in the presence of salt for therapeutic application. PapN was calcium- and magnesium-resistant in a physiological condition, especially against Gram-negative bacteria, implying that it can be a potent candidate as peptide antibiotics.

Keywords

References

  1. E. Guani-Guerra, T. Santos-Mendoza , S. O. Lugo-Reyes, and L. M. Teran, Clin Immunol. 135, 1 (2010) https://doi.org/10.1016/j.clim.2009.12.004
  2. P. Bulet, R. Stocklin, and L. Menin, Immunol Rev. 198, 169 (2004) https://doi.org/10.1111/j.0105-2896.2004.0124.x
  3. R. E. Hancock, and R. Lehrer, Trends Biotechnol. 16, 82 (1998) https://doi.org/10.1016/S0167-7799(97)01156-6
  4. S. E. Blondelle, K. Lohner, and M. Aguilar, Biochem Biophys Acta. 1462, 89 (1999) https://doi.org/10.1016/S0005-2736(99)00202-3
  5. R. E. Hancock, and H. G. Sahl, Nat Biotechnol. 24, 1551 (2006) https://doi.org/10.1038/nbt1267
  6. K. A. Brogden, Nat Rev Microbial. 3, 238 (2005) https://doi.org/10.1038/nrmicro1098
  7. E. Lee, J.-K. Kim, S. Shin, K.-W. Jeong, A. Shin, J. Lee, D. G. Lee, J.-S. Hwang, and Y. Kim, Biochem Biophys Acta. 1828, 271 (2013) https://doi.org/10.1016/j.bbamem.2012.10.028
  8. S. R. Kim, M. Y. Hong, S. W. Park, K. H. Choi, E. Y. Yun, T. W. Goo, S. W. Kang, H. J. Suh, I. Kim, and J. S. Hwang Mol. Cells 29, 419 (2010) https://doi.org/10.1007/s10059-010-0050-y
  9. J.-K. Kim, E. Lee, S. Shin, K.-W. Jeong, J.-Y. Lee, S.-Y. Bae, S.-H. Kim, J. Lee, S. R. Kim, D. G. Lee, J.-S, Hwang, and Y. Kim, J. Biol. Chem. 286, 41296 (2011) https://doi.org/10.1074/jbc.M111.269225
  10. E. Lee, J.-K. Kim, D. Jeon, K.-W. Jeong, A. Shin, and Y. Kim, Scientific reports. 5, 12048 (2015) https://doi.org/10.1038/srep12048
  11. A. Derome, and M. Williamson, J.Magn. Reson. 88, 177 (1990)
  12. A. Bax and D. G. Davis, J. Magn. Reson. 65, 355 (1985)
  13. A. Bax and D. G. Davis, J. Magn. Reson. 64, 207(1985)
  14. D. Marion and K. Wuthrich, Biochem Biophys Res Commun. 113, 967 (1983) https://doi.org/10.1016/0006-291X(83)91093-8
  15. F. Delaglio, S. Grzesiak, G. Vuister, G. Zhu, J. Pfeifer, and A. Bax, J. Biomol. NMR. 6, 277 (1995)
  16. T. D. Goddard and D. G. Kneller, Sparky 3, University of California, SanFransisco, CA.
  17. P. Guntert, Methods Mol Bio. 278, 353 (2004)
  18. J.-K. Kim, E. Lee, K.-W. Jeong, and Y. Kim J. Kor. Mag. Reson. Soc. 15, 1 (2011)
  19. K. F. Morris and C. S. Johnson, J. Am. Chem.114, 3139 (1992) https://doi.org/10.1021/ja00034a071
  20. A. M. Cole, R. O. Darouiche, D. Legarda, N. Connell, and G. Diamond Antimicrob. Agents. Chemother. 44, 2039 (2000) https://doi.org/10.1128/AAC.44.8.2039-2045.2000
  21. W. Kim, J. Rhee, J. Yi, B. Lee, and W. Son, J. Kor. Mag. Reson. Soc. 18, 36 (2014) https://doi.org/10.6564/JKMRS.2014.18.1.036
  22. K. Lee and J. Suh, J. Kor. Mag. Reson. Soc. 19, 42 (2015) https://doi.org/10.6564/JKMRS.2015.19.1.042
  23. D. S. Wishart, B. D. Sykes, and F. M. Richards, Biochemistry. 31, 1647-1651 (1992) https://doi.org/10.1021/bi00121a010