Design of antimicrobial peptides: Progress made with human cathelicidin LL-37

Guangshun Wang, Jayaram Lakshmaiah Narayana, Biswajit Mishra, Yingxia Zhang, Fangyu Wang, Chunfeng Wang, D. Zarena, Tamara Lushnikova, Xiuqing Wang

Research output: Chapter in Book/Report/Conference proceedingChapter

6 Scopus citations

Abstract

The incorporation of the innate immune system into humans is essential for survival and health due to the rapid replication of invading microbes and the delayed action of the adaptive immune system. Antimicrobial peptides are important components of human innate immunity. Over 100 such peptides have been identified in various human tissues. Human cathelicidin LL-37 is best studied, and there has been a growing interest in designing new peptides based on LL-37. This chapter describes the alternative processing of the human cathelicidin precursor, protease digestion, and lab cutting of LL-37. Both a synthetic peptide library and structure-based design are utilized to identify the active regions. Although challenging, the determination of the 3D structure of LL-37 enabled the identification of the core antimicrobial region. The minimal region of LL-37 can be function-dependent. We discuss the design and potential applications of LL-37 into antibacterial, antibiofilm, antiviral, antifungal, immune modulating, and anticancer peptides. LL-37 has been engineered into 17BIPHE2, a stable, selective, and potent antimicrobial, antibiofilm, and anticancer peptide. Both 17BIPHE2 and SAAP-148 can eliminate the ESKAPE pathogens and show topical in vivo antibiofilm efficacy. Also discussed are other application strategies, including peptide formulation, antimicrobial implants, and peptide-inducing factors such as vitamin D and sunlight. Finally, we summarize what we learned from peptide design based on human LL-37.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages215-240
Number of pages26
DOIs
StatePublished - Jan 1 2019

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1117
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Anticancer peptides
  • Antimicrobial peptides
  • Antiviral peptides
  • Cathelicidins
  • LL-37
  • Peptide design

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Wang, G., Narayana, J. L., Mishra, B., Zhang, Y., Wang, F., Wang, C., Zarena, D., Lushnikova, T., & Wang, X. (2019). Design of antimicrobial peptides: Progress made with human cathelicidin LL-37. In Advances in Experimental Medicine and Biology (pp. 215-240). (Advances in Experimental Medicine and Biology; Vol. 1117). Springer New York LLC. https://doi.org/10.1007/978-981-13-3588-4_12