title: Basic peptide-morpholino oligomer conjugate that is very effective in killing bacteria by gene-specific and nonspecific modes.
abstract: Basic peptides covalently linked to nucleic acids, or chemically modified nucleic acids, enable the insertion of such a conjugate into bacteria grown in liquid medium and mammalian cells in tissue culture. A unique peptide, derived from human T cells, has been employed in a chemical synthesis to make a conjugate with a morpholino oligonucleotide. This new conjugate is at least 10- to 100-fold more effective than previous peptides used in altering the phenotype of host bacteria if the external guide sequence methodology is employed in these experiments. Bacteria with target genes expressing chloramphenicol resistance, penicillin resistance, or gyrase A function can effectively be reduced in their expression and the host cells killed. Several bacteria are susceptible to this treatment, which has a broad range of potency. The loss in viability of bacteria is not due only to complementarity with a target RNA and the action of RNase P, but also to a non-gene-specific tight binding of the complexed nontargeted RNA to the basic polypeptide-morpholino oligonucleotide.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Wesolowski
authors.forename: Hyun Seop
authors.initials: HS
authors.lastname: Tae
authors.forename: Neeru
authors.initials: N
authors.lastname: Gandotra
authors.forename: Paula
authors.initials: P
authors.lastname: Llopis
authors.forename: Ning
authors.initials: N
authors.lastname: Shen
authors.forename: Sidney
authors.initials: S
authors.lastname: Altman
mesh_terms: D057846:Cell-Penetrating Peptides / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects*; D019793:Fluorescein; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006801:Humans; D060172:Morpholinos / Q000378:metabolism / Q000494:pharmacology*; D046912:Multiprotein Complexes / Q000096:biosynthesis / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000737:chemistry
chemical_list: D057846:Cell-Penetrating Peptides; D060172:Morpholinos; D046912:Multiprotein Complexes; D019793:Fluorescein