PMID:6389761
| Citation |
Payne, JW, Morley, JS, Armitage, P and Payne, GM (1984) Transport and hydrolysis of antibacterial peptide analogues in Escherichia coli: backbone-modified aminoxy peptides.J. Gen. Microbiol. 130:2253-65 |
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| Abstract |
Aminoxy analogues of di- and tripeptides in which the peptide linkage is replaced by -CO-NHO-, either as an L- or D-2-aminoxypropionic acid (L or D-OAla) residue, have been examined for antibacterial activity in vitro and for uptake into Escherichia coli. Isolation of analogue-resistant mutants and cross-resistance tests with peptide-transport mutants indicate that all three peptide permeases can transport these backbone-modified analogues. A number of mutants with defects in particular intracellular peptidases show decreased sensitivity to a range of these analogues, allowing identification of the enzymes responsible for their cleavage and confirming that hydrolysis is essential for their toxicity. Ala-OAla is a bacteriostatic agent that inhibits nucleic acid and protein synthesis within 1 min of being added to an exponentially growing culture. In crude extracts Ala-OAla inhibits transaminase activity but only after liberation of OAla by endogenous peptidases. These antibacterial agents illustrate an approach to drug targeting in which peptide carriers are used to promote uptake of essentially impermeant toxic moieties. |
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| Keywords |
Alanine; Anti-Bacterial Agents; Biological Transport; Escherichia coli; Hydrolysis; Membrane Transport Proteins; Peptide Hydrolases; Peptides; Salmonella typhimurium |
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Main Points of the Paper
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Materials and Methods Used
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Phenotype Annotations
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| Phenotype of | Taxon Information | Genotype Information (if known) | Condition Information | OMP ID | OMP Term Name | ECO ID | ECO Term Name | Notes | Status |
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a mutation or genetic difference within a strain |
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Resistance to alanyl-2-aminopropanoate. |
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a mutation or genetic difference within a strain |
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Lysyl-2-aminooxypronate Resistance |
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a mutation or genetic difference within a strain |
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Alafosfalin resistance |
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Notes
Needs OMP term, resistance to whatever this is and ECO term ID
References
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