Combined effect of a peptide-morpholino oligonucleotide conjugate and a cell-penetrating peptide as an antibiotic

Proc Natl Acad Sci U S A. 2013 May 21;110(21):8686-9. doi: 10.1073/pnas.1306911110. Epub 2013 May 6.

Abstract

A cell-penetrating peptide (CPP)-morpholino oligonucleotide (MO) conjugate (PMO) that has an antibiotic effect in culture had some contaminating CPPs in earlier preparations. The mixed conjugate had gene-specific and gene-nonspecific effects. An improved purification procedure separates the PMO from the free CPP and MO. The gene-specific effects are a result of the PMO, and the nonspecific effects are a result of the unlinked, unreacted CPP. The PMO and the CPP can be mixed together, as has been shown previously in earlier experiments, and have a combined effect as an antibiotic. Kinetic analysis of these effects confirm this observation. The effect of the CPP is bacteriostatic. The effect of the PMO appears to be bacteriocidal. An assay for mutations that would alter the ability of these agents to affect bacterial viability is negative.

Keywords: EGS technology; RNase P; gram-negative bacteria; gram-positive bacteria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents* / chemical synthesis
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Bacteria / growth & development*
  • Bacterial Infections / drug therapy
  • Bacterial Infections / microbiology
  • Cell-Penetrating Peptides* / chemical synthesis
  • Cell-Penetrating Peptides* / chemistry
  • Cell-Penetrating Peptides* / pharmacology
  • Morpholinos* / chemical synthesis
  • Morpholinos* / chemistry
  • Morpholinos* / pharmacology

Substances

  • Anti-Bacterial Agents
  • Cell-Penetrating Peptides
  • Morpholinos