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Are highly morphed peptide frameworks lurking silently in microbial genomes valuable as next generation antibiotic scaffolds?

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Abstract

Antibiotics are a therapeutic class that, once deployed, select for resistant bacterial pathogens and so shorten their useful life cycles. As a consequence new versions of antibiotics are constantly needed. Among the antibiotic natural products, morphed peptide scaffolds, converting conformationally mobile, short-lived linear peptides into compact, rigidified small molecule frameworks, act on a wide range of bacterial targets. Advances in bacterial genome mining, biosynthetic gene cluster prediction and expression, and mass spectroscopic structure analysis suggests many more peptides, modified both in side chains and peptide backbones, await discovery. Such molecules may turn up new bacterial targets and be starting points for combinatorial or semisynthetic manipulations to optimize activity and pharmacology parameters.

Graphical abstract: Are highly morphed peptide frameworks lurking silently in microbial genomes valuable as next generation antibiotic scaffolds?

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Publication details

The article was received on 31 Jan 2017 and first published on 17 May 2017


Article type: Viewpoint
DOI: 10.1039/C7NP00011A
Citation: Nat. Prod. Rep., 2017, Advance Article
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    Are highly morphed peptide frameworks lurking silently in microbial genomes valuable as next generation antibiotic scaffolds?

    C. T. Walsh, Nat. Prod. Rep., 2017, Advance Article , DOI: 10.1039/C7NP00011A

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