title: Antimicrobial potency and selectivity of simplified symmetric-end peptides.
abstract: Because antimicrobial peptides (AMPs) are potentially useful for the treatment of multidrug-resistant infections, more attention is being paid to the structural modification and structure-function relationship of both naturally occurring and synthetic AMPs. Previous studies indicated that Protegrin-1 (PG-1), isolated from porcine leukocytes, exhibited considerable antimicrobial activity and cytotoxicity. The β-turn of PG-1 floated on the surface of bacterial membrane, while its β-strand inserted into the bacterial membrane and formed pores that were dedicated to producing cytotoxicity. For reducing cytotoxicity and improving cells selectivity, we designed a series of simplified symmetric-end peptides by combining the β-turn of PG-1 with simple amino acid repeat sequences. The sequence of designed symmetric-end peptides is (XR)nH(RX)n, (n = 1,2; X represents I, F, W and P; H represents CRRRFC). The symmetric-end peptides displayed antimicrobial activity against both gram-positive and gram-negative bacteria. In particular, (XR)2H(RX)2 (X here is I, F and W) showed greater antimicrobial potency than PG-1. Hemolysis activity and cytotoxicity, detected by using human red blood cells (RBCs) and human embryonic lung fibroblasts MRC-5 cells, were observably lower than the native peptide PG-1. (IR)2H(RI)2 (IR2), folded into β-sheet structures, displayed the highest therapeutic index, suggesting its great cell selectivity. The fluorescence spectroscopy, flow cytometry, and electron microscopy observation indicated that IR2 exhibited great membrane penetration potential by inducing membrane blebbing, disruption and lysis. Collectively, generating symmetric-end β-sheet peptides is a promising strategy for designing effective AMPs with great antimicrobial activities and cell selectivity.
authors: Laboratory of Molecular Nutrition and Immunity, The Institute of Animal Nutrition, Northeast Agricultural University, Harbin, PR China.
authors: Na
authors: N
authors: Dong
authors: Laboratory of Molecular Nutrition and Immunity, The Institute of Animal Nutrition, Northeast Agricultural University, Harbin, PR China.
authors: Xin
authors: X
authors: Zhu
authors: Laboratory of Molecular Nutrition and Immunity, The Institute of Animal Nutrition, Northeast Agricultural University, Harbin, PR China.
authors: Shuli
authors: S
authors: Chou
authors: Laboratory of Molecular Nutrition and Immunity, The Institute of Animal Nutrition, Northeast Agricultural University, Harbin, PR China. Electronic address: asshan@neau.edu.cn.
authors: Anshan
authors: A
authors: Shan
authors: Laboratory of Molecular Nutrition and Immunity, The Institute of Animal Nutrition, Northeast Agricultural University, Harbin, PR China.
authors: Weizhong
authors: W
authors: Li
authors: The State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, PR China.
authors: Junguang
authors: J
authors: Jiang
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002942:Circular Dichroism; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000648:ultrastructure; D005434:Flow Cytometry; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008564:Membrane Potentials / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D012492:Salts / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D000890:Anti-Infective Agents; D010455:Peptides; D012492:Salts
keywords: Bactericidal mechanism; Cell selectivity; Hemolysis; Membrane; Symmetric-end peptides