Cathelicidins are a group of cationic host defense peptides with pluripotent immunomodulatory activities. We recently identified fowlicidin-1, a chicken cathelicidin possessing broad-spectrum antibacterial and LPS-neutralizing activities but with considerable toxicity toward mammalian cells. NMR spectroscopy revealed that fowlicidin-1 mainly adopts an α-helical conformation with glycine-induced kink in the center and a short flexible unstructured region at the N-terminal end. To reveal functional significance of different structural regions and identify peptide analog(s) with enhanced therapeutic potential, a series of deletion and substitution analogs of fowlicidin -1 were synthesized. Eight amino acids (residues 16–23) at the C-terminal end were found to be critically involved in bacterial killing, LPS binding and cytotoxicity. We also revealed that the N-terminal unstructured segment (residues 1–5) plays a minimum role in antibacterial and LPS-neutralizing activities. Removal of valine at position 5 reduced the cytotoxicity by 4-fold while retaining a similar antibacterial potency to the parent peptide. However, omission of tryptophan at position 6 resulted in at least 4-fold reduction in bacteria-killing efficiency, indicating the critical involvement of tryptophan. Taken together, fowlicidin-1(6–26) represents a short peptide analog with excellent potential to be explored as a novel antimicrobial. This project was supported by Oklahoma Center for the Advancement of Science and Technology, Oklahoma Agricultural Experiment Station and HHMI-Undergraduate Research Scholarship.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.