title: Truncated and constrained helical analogs of antimicrobial esculentin-2EM.
abstract: Esculentin-2EM is a 37-residue, cationic, amphipathic, α-helical antimicrobial peptide isolated from a Korean frog, Glandirama emeljanovi. Many studies revealed that truncation of this peptide results in substantial decreases in its antimicrobial activity. Lee and his colleagues have recently reported that a 23-residue esculentin-2EM analog containing a tryptophanyl substitution at position 16 showed a significant recovery of the antimicrobial activity of the parent peptide. Here we report a new series of 15-residue esculentin-2EM analogs which are constrained into an α-helical conformation via an oct-4-enyl cross-link. The resulting 'stapled' derivatives displayed remarkable increases not only in antimicrobial activity but also in helical content and protease resistance compared to Lee's original 23-residue esculentin-2EM analog. The preliminary data obtained in this work strongly supports the potential of our strategy for the development of a new class of peptide antibiotics.
authors.affiliation: College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Thanh Kim
authors.initials: TK
authors.lastname: Pham
authors.forename: Do-Hee
authors.initials: DH
authors.lastname: Kim
authors.forename: Bong-Jin
authors.initials: BJ
authors.lastname: Lee
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001001:Anura / Q000378:metabolism; D002942:Circular Dichroism; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary
chemical_list: D029845:Amphibian Proteins; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; C000589838:esculentin-2EM peptide, Glandirama emeljanovi
keywords: Antimicrobial peptides; Esculentin-2EM; Proteolytic resistance; Stapled peptides; α-Helix