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Optimization of sequence and chiral content enhances therapeutic potential of tilapia piscidin peptides.
Hsu, Po-Hsien; Hazam, Prakash Kishore; Huang, Yi-Ping; Yeh, Jih-Chao; Chen, Yun-Ru; Li, Chao-Chin; Chang, Chi-Fon; Liou, Je-Wen; Chen, Jyh-Yih.
Afiliación
  • Hsu PH; Institute of Fisheries Science, National Taiwan University, 1 Roosevelt Road, Sec. 4, Taipei, 106, Taiwan.
  • Hazam PK; Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Rd., Jiaushi, Ilan, 262, Taiwan.
  • Huang YP; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • Yeh JC; Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Rd., Jiaushi, Ilan, 262, Taiwan.
  • Chen YR; Academia Sinica Protein Clinic, Institute of Biological Chemistry, Academia Sinica, 128, Academia Road, Section 2, Nankang District, Taipei, 115, Taiwan.
  • Li CC; Institute of Cellular and Organismic Biology, Academia Sinica, Nankang, Taipei, 115, Taiwan.
  • Chang CF; Genomics Research Center, Academia Sinica, Taipei, Taiwan. Electronic address: chifon@gate.sinica.edu.tw.
  • Liou JW; Department of Biochemistry, School of Medicine, Tzu Chi University, 701, Sec.3, Chung-Yang Rd, Hualien, 970, Taiwan. Electronic address: jwliou@mail.tcu.edu.tw.
  • Chen JY; Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Rd., Jiaushi, Ilan, 262, Taiwan; The IEGG and Animal Biotechnology Center and the Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, 402, Taiwan. Electr
Eur J Med Chem ; 265: 116083, 2024 Feb 05.
Article en En | MEDLINE | ID: mdl-38150960
ABSTRACT
Because antimicrobial peptides (AMPs) often exhibit broad-spectrum bactericidal potency, we sought to develop peptide-based antimicrobials for potential clinical use against drug-resistant pathogens. To accomplish this goal, we first optimized the amino acid sequence of a broad-spectrum AMP known as Tilapia Piscidin 4 (TP4). Then, we used the optimized sequence to create a pair of heterochiral variants (TP4-α and TP4-ß) with different percentages of D-enantiomers, as poly-L peptides often exhibit poor pharmacokinetic profiles. The conformations of the peptide pair exhibited inverted chirality according to CD and NMR spectroscopic analyses. Both heterochiral peptides displayed enhanced stability and low hemolysis activities. Irrespective of their different d-enantiomer contents, both heterochiral peptides exhibited bactericidal activities in the presence of human serum or physiological enzymes. However, the peptide with higher d-amino acid content (TP4-ß) caused better bacterial clearance when tested in mice infected with NDM-1 K. pneumoniae. In addition, we observed a relatively higher hydrogen bonding affinity in a simulation of the interaction between TP4-ß and a model bacterial membrane. In sum, our results demonstrate that the current design strategy may be applicable for development of new molecules with enhanced stability and in vivo antimicrobial activity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tilapia / Antiinfecciosos Límite: Animals / Humans Idioma: En Revista: Eur J Med Chem Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Francia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tilapia / Antiinfecciosos Límite: Animals / Humans Idioma: En Revista: Eur J Med Chem Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Francia