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Contributed by Sidney Altman, August 16, 2011 (sent for review July 13, 2011)
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.
Footnotes
↵1Present address: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.
↵2Present address: Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
- ↵3To whom correspondence should be addressed. E-mail: sidney.altman{at}yale.edu.
Author contributions: S.A. designed research; D.W., H.S.T., N.G., P.L., and N.S. performed research; S.A. analyzed data; and S.A. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1112561108/-/DCSupplemental.
Basic peptide-morpholino oligomer conjugate that is very effective in killing bacteria by gene-specific and nonspecific modes
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