Basic peptide-morpholino oligomer conjugate that is very effective in killing bacteria by gene-specific and nonspecific modes

Donna Wesolowski, Hyun Seop Tae, Neeru Gandotra, Paula Llopis, Ning Shen, Sidney Altman

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)16582-16587
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number40
DOIs
StatePublished - Oct 4 2011
Externally publishedYes

Fingerprint

Morpholinos
Bacteria
Peptides
Nucleic Acids
Genes
Ribonuclease P
Chloramphenicol Resistance
RNA
Microbial Viability
Penicillin Resistance
T-Lymphocytes
Phenotype

Keywords

  • Gene expression
  • Pathogenic bacteria

ASJC Scopus subject areas

  • General

Cite this

Basic peptide-morpholino oligomer conjugate that is very effective in killing bacteria by gene-specific and nonspecific modes. / Wesolowski, Donna; Tae, Hyun Seop; Gandotra, Neeru; Llopis, Paula; Shen, Ning; Altman, Sidney.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 40, 04.10.2011, p. 16582-16587.

Research output: Contribution to journalArticle

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