title: Improvement of in vivo antimicrobial activity of HBcARD peptides by D-arginine replacement.
abstract: We previously identified a novel antimicrobial peptide with a broad spectrum bactericidal activity from human hepatitis B virus (HBV) core protein (HBc) arginine-rich domain (ARD). We compared the antimicrobial activities of HBcARD peptides from different hepadnaviruses which share similar amino acid sequences. In general, mammalian HBcARD peptides exhibited stronger antimicrobial activity than avian peptides. Using the strategy of D-amino acid substitutions, we improved the antimicrobial efficacy of human HBcARD peptide. This D-HBcARD peptide was much more resistant than L-HBcARD peptide to proteolytic degradation in vitro. Moreover, this D-HBcARD peptide maintained similar minimal bactericidal concentrations (MBC) against tested bacteria, and showed very low hemolytic activity. In the Staphylococcus aureus-infected mouse model, this D-HBcARD peptide was more protective than the L-HBcARD peptide. Repeated treatments with either L- or D-HBcARD peptides induced no significant immunogenicity. New derivatives of HBcARD peptides could serve as alternatives to the conventional antibiotics in clinical medicine in the future.
authors.affiliation: Institute of Biomedical Sciences (IBMS), Academia Sinica, 128 Academia Rd. Sec 2, Nangung, Taipei, Taiwan.
authors.forename: Heng-Li
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences (IBMS), Academia Sinica, 128 Academia Rd. Sec 2, Nangung, Taipei, Taiwan.|Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.|Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Su
authors.affiliation: Institute of Biomedical Sciences (IBMS), Academia Sinica, 128 Academia Rd. Sec 2, Nangung, Taipei, Taiwan. cshih@ibms.sinica.edu.tw.
authors.forename: Chiaho
authors.initials: C
authors.lastname: Shih
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000378:metabolism*; D001120:Arginine / Q000235:genetics*; D004195:Disease Models, Animal; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000378:metabolism*; D008813:Mice, Inbred ICR; D050296:Microbial Viability / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D006512:Hepatitis B Core Antigens; D010455:Peptides; D001120:Arginine
keywords: Animal model; Antimicrobial activity; D-amino acid replacement; HBcARD peptide; Hepadnaviruses