title: Role of β-naphthylalanine end-tags in the enhancement of antiendotoxin activities: Solution structure of the antimicrobial peptide S1-Nal-Nal in complex with lipopolysaccharide.
abstract: Lipopolysaccharide (LPS, endotoxin) is the major component of Gram-negative bacterial outer surface membrane. LPS released from bacteria into bloodstream during infection may cause serious unwanted stimulation of host's immune system and lead to septic shock of the patient. Recently, we have developed a strategy to increase salt resistance and LPS neutralization of short antimicrobial peptides by adding β-naphthylalanine end-tags to their termini. Herein, correlations between membrane immersion depth, orientation, and antiendotoxin activities of the antimicrobial peptides S1 and S1-Nal-Nal have been investigated via solution structure, paramagnetic resonance enhancement, and saturation transfer difference NMR studies. Unlike the parent peptide S1, S1-Nal-Nal rotated its two terminal β-naphthylalanine residues into the hydrophobic lipid A motif of LPS micelles. The LPS-induced inflammation may then be prohibited by the blocked lipid A motif.
authors.affiliation: Institute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Hui-Yuan
authors.initials: HY
authors.lastname: Yu
authors.affiliation: Institute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Chen
authors.affiliation: Institute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, Taiwan; Department of Neurology, National Taiwan University Hospital Hsinchu Branch, Hsinchu 300, Taiwan.
authors.forename: Bak-Sau
authors.initials: BS
authors.lastname: Yip
authors.affiliation: Institute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Siou-Ying
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Institute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Hsiu-Ju
authors.initials: HJ
authors.lastname: Wei
authors.affiliation: Institute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Ya-Han
authors.initials: YH
authors.lastname: Chih
authors.affiliation: Institute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Kuan-Hao
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Institute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, Taiwan. Electronic address: jwcheng@life.nthu.edu.tw.
authors.forename: Jya-Wei
authors.initials: JW
authors.lastname: Cheng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D000931:Antidotes / Q000138:chemical synthesis* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000931:Antidotes; D023181:Antimicrobial Cationic Peptides; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha
keywords: Antiendotoxin; Antimicrobial peptide; End-tags; NMR; β-Naphthylalanine