title: Molecular design of LPS-binding peptides.
abstract: Lipopolysaccharide (LPS), a major constituent of the outer membrane of Gram-negative bacteria, is highly toxic and can cause sepsis or septic shock. Therefore, detection of LPS and the ability to neutralize its toxicity is important. We previously obtained a strong LPS-binding peptide, Li5-001, using the phage display method (Matsumoto et al., 2010. J. Microbiol. Methods. 82, 54-58). We modified the sequence the amino acid sequence of this peptide (KNYSSSISSIHAC), by replacing and deleting amino acids to obtain higher LPS-binding affinity and greater resistance to protease digestion. Consequently we obtained a dodecapeptide, Li5-025 (K'YSSSISSIRAC', K' and C' are D-forms of K and C, respectively) which showed a high affinity for LPS, approximately 1000 folds higher affinity than Li5-001 and Kd value of 0.01 nM. By replacing both N- and C-terminal amino acids from L-type to D-type, the peptide was rendered resistant to protease digestion without altering its overall binding capacity.
authors.affiliation: Peptide Door Co., Ltd., Sangyosozo-kan #204, Shimonojo 936-14, Takasaki, Gunma 370-0854, Japan.
authors.forename: Masatsugu Matt
authors.initials: MM
authors.lastname: Suzuki
authors.forename: Megumi
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Ochiai
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Horiuchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Niwa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Omi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Takagi
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D008070:Lipopolysaccharides / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D008070:Lipopolysaccharides; D019151:Peptide Library; D010455:Peptides; D010447:Peptide Hydrolases