title: RTD-1mimic containing γPNA scaffold exhibits broad-spectrum antibacterial activities.
abstract: Macrocyclic peptides with multiple disulfide cross-linkages, such as those produced by plants and those found in nonhuman primates, as components of the innate immunity, hold great promise for molecular therapy because of their broad biological activities and high chemical, thermal, and enzymatic stability. However, for some, because of their intricate spatial arrangement and elaborate interstrand cross-linkages, they are difficult to prepare de novo in large quantities and high purity, due to the nonselective nature of disulfide-bond formation. We show that the disulfide bridges of RTD-1, a member of the θ-defensin subfamily, could be replaced with noncovalent Watson-Crick hydrogen bonds without significantly affecting its biological activities. The work provides a general strategy for engineering conformationally rigid, cyclic peptides without the need for disulfide-bond reinforcement.
authors.affiliation: Department of Chemistry and Center for Nucleic Acids Science and Technology (CNAST), Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Rapireddy
authors.forename: Linda
authors.initials: L
authors.lastname: Nhon
authors.forename: Robert E
authors.initials: RE
authors.lastname: Meehan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Franks
authors.forename: Donna Beer
authors.initials: DB
authors.lastname: Stolz
authors.forename: Dat
authors.initials: D
authors.lastname: Tran
authors.forename: Michael E
authors.initials: ME
authors.lastname: Selsted
authors.forename: Danith H
authors.initials: DH
authors.lastname: Ly
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D020135:Peptide Nucleic Acids / Q000737:chemistry / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D020135:Peptide Nucleic Acids; D010456:Peptides, Cyclic