title: Novel gratisin derivatives with high antimicrobial activity and low hemolytic activity.
abstract: The substitution of each constituent amino acid residue of gratisin (GR) with Ala residue indicated that each side chain structure of the constituent amino acid residues affect largely the antibiotic and hemolytic activities of GR. Among them, the substitution of Pro residues at positions 5 and 5' with a cationic amino acid residues (Lys and Arg) results the high antibiotic activity and the low toxicity against human blood cells. Thus, we have found a novel position on the scaffold of GR at Pro(5,5') residues whose modification will significantly lower the unwanted hemolytic activity and enhance the desired antibiotic activity.
authors.affiliation: Department of Chemistry, Toho University, Funabashi, Chiba 274-8510, Japan. tamaki@chem.sci.toho-u.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Tamaki
authors.forename: Yukie
authors.initials: Y
authors.lastname: Imazeki
authors.forename: Aya
authors.initials: A
authors.lastname: Shirane
authors.forename: Kenta
authors.initials: K
authors.lastname: Fujinuma
authors.forename: Mitsuno
authors.initials: M
authors.lastname: Shindo
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kimura
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Uchida
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002942:Circular Dichroism; D006461:Hemolysis; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D010456:Peptides, Cyclic; C033282:gratisin