期刊
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
卷 1798, 期 10, 页码 1913-1925出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamem.2010.06.026
关键词
Piscidin 1; Antimicrobial peptide; Peptoid residue; Cell selectivity; Structure; NMR
资金
- Ministry of Education, Science and Technology [2009-0076064]
- Biogreen 21 program, Rural Development Administration [20080401-034-017]
- National Research Foundation of Korea [2009-0076064] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- Rural Development Administration (RDA), Republic of Korea [PJ00711520101136300] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Piscidin 1 (Pis-1) is a novel cytotoxic peptide with a cationic a-helical structure isolated from the mast cells of hybrid striped bass. In our previous study, we showed that Pis-1[PG] with a substitution of Pro(8) for Gly(8) in Pis-1 had higher bacterial cell selectivity than Pis-1. We designed peptoid residue-substituted peptide, Pis-1 [NkG], in which Gly(8) of Pis-1 was replaced with Nlys (Lys peptoid residue). Pis-1[NkG] had higher antibacterial activity and lower cytotoxicity against mammalian cells than Pis-1 and Pis-1[PG]. We determined the tertiary structure of Pis-1[PG] and Pis-1[NkG] in the presence of DPC micelles by NMR spectroscopy. Both peptides had a three-turn helix in the C-terminal region and a bent structure in the center. Pis-1[PG] has a rigid bent structure at Pro(8) whereas Pis-1[NkG] existed as a dynamic equilibrium of two conformers with a flexible hinge structure at Nlys(8). Depolarization of the membrane potential of Staphylococcus aureus and confocal laser-scanning microscopy study revealed that Pis-1[NkG] effectively penetrated the bacterial cell membrane and accumulated in the cytoplasm, whereas Pis-1[PG] did not penetrate the membrane but remained outside or on the cell surface. Introduction of a lysine peptoid at position 8 of Pis-1 provided conformational flexibility and increased the positive charge at the hinge region; both factors facilitated penetration of the bacterial cell membrane and conferred bacterial cell selectivity on Pis-1[NkG]. (C) 2010 Elsevier B.V. All rights reserved.
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