Structure and Activity of a Selective Antibiofilm Peptide SK-24 Derived from the NMR Structure of Human Cathelicidin LL-37

Authors

Yingxia Zhang, University of Nebraska Medical Center
Jayaram Lakshmaiah Narayana, University of Nebraska Medical Center
Qianhui Wu, University of Nebraska Medical Center
Xiangli Dang, University of Nebraska Medical Center
Guangshun Wang, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

Pharmaceuticals

Publication Date

2021

Volume

14

Abstract

The deployment of the innate immune system in humans is essential to protect us from infection. Human cathelicidin LL-37 is a linear host defense peptide with both antimicrobial and immune modulatory properties. Despite years of studies of numerous peptides, SK-24, corresponding to the long hydrophobic domain (residues 9–32) in the anionic lipid-bound NMR structure of LL-37, has not been investigated. This study reports the structure and activity of SK-24. Interestingly, SK-24 is entirely helical (~100%) in phosphate buffer (PBS), more than LL-37 (84%), GI-20 (75%), and GF-17 (33%), while RI-10 and 17BIPHE2 are essentially randomly coiled (helix%: 7–10%). These results imply an important role for the additional N-terminal amino acids (likely E16) of SK-24 in stabilizing the helical conformation in PBS. It is proposed herein that SK-24 contains the minimal sequence for effective oligomerization of LL-37. Superior to LL-37 and RI-10, SK-24 shows an antimicrobial activity spectrum comparable to the major antimicrobial peptides GF-17 and GI-20 by targeting bacterial membranes and forming a helical conformation. Like the engineered peptide 17BIPHE2, SK-24 has a stronger antibiofilm activity than LL-37, GI-20, and GF-17. Nevertheless, SK-24 is least hemolytic at 200 µM compared with LL-37 and its other peptides investigated herein. Combined, these results enabled us to appreciate the elegance of the long amphipathic helix SK-24 nature deploys within LL-37 for human antimicrobial defense. SK-24 may be a useful template of therapeutic potential

DOI Link

10.3390/ph14121245

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Zhang, Yingxia; Narayana, Jayaram Lakshmaiah; Wu, Qianhui; Dang, Xiangli; and Wang, Guangshun, "Structure and Activity of a Selective Antibiofilm Peptide SK-24 Derived from the NMR Structure of Human Cathelicidin LL-37" (2021). Journal Articles: Pathology and Microbiology. 81.
https://digitalcommons.unmc.edu/com_pathmicro_articles/81