[March 28. 2019] NMR Structural Studies of engineered novel antimicrobial peptides

NMR Structural Studies of engineered novel antimicrobial peptides

  Since the discovery of penicillin, antibiotics have brought benefits such as prolonging human life, treating bacterial infections as well as promoting animal growth, but misuse and abuse of antibiotics have caused serious public health problems and economic losses. Thus, antibiotics that work in a completely different way from conventional antibiotics have become necessary, and long-term solutions to these problems include antimicrobial peptides produced by all organisms, from bacteria to vertebrates and invertebrates.

  We have successfully identified the structure and activity of Lactophoricin (LPcin), an antimicrobial peptide found in bovine milk, through expression using recombinant DNA technology, purification using various biophysical techniques, and structural studies using liquid/solid-state NMR [1, 2]. Based on this LPcin, we constructed a total of 20 analogs library through conservative sequence modification to develop new antimicrobial peptides with shorter length and improved antimicrobial activity than conventional LPcin. Among them, six new antimicrobial peptides were selected through bacterial killing assays and growth inhibition assays, and each peptide was obtained a high purity, sufficient amount for structural studies by optimization of the expression and purification process [3, 4]. In addition, each peptide identified its potential as a new antibiotic through hemolysis assay and cytotoxicity assay, and to investigate the relationship between active-structure by conducting a 3D topology structure study using liquid/solid-state NMR. 

[1] Park TJ., Kim JS., Ahn HC. and Kim Y., “Solution and Solid-State NMR Structural Studies of Antimicrobial Peptides LPcin-I and LPcin-II”, Biophysical Journal, Vol. 101, (2011), pp 1193–1201.

[2] Jeong JH, Kim JS, Choi SS. and Kim Y., “NMR Structural Studies of Antimicrobial Peptides: LPcin Analogs”, Biophysical Journal, Vol. 110, (2016), pp 423–430.

[3] Kim JS., Jeong JH. and Kim Y., “Design, Characterization, and Antimicrobial Activity of a Novel Antimicrobial Peptide Derived from Bovine Lactophoricin” J. Microbiol. Biotechnol. Vol. 27, (2017), 759–767

[4] Kim Y., Kim JS., Jeong JH., “Design and NMR Structural Studies of new Antimicrobial Peptides with higher activity” Biophysical Journal, Vol. 114, (2018), pp 159a.