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

Author:
Wesolowski, Donna, Alonso, Dulce, Altman, Sidney
Source:
Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.21 pp. 8686-8689
ISSN:
0027-8424
Subject:
antibiotics, mutation, oligonucleotides, viability
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.
Agid:
1736823