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Synthesis of Hybrid Cyclopeptides through Enzymatic Macrocyclization.

ABSTRACT: Natural products comprise a diverse array of molecules, many of which are biologically active. Most natural products are derived from combinations of polyketides, peptides, sugars, and fatty-acid building blocks. Peptidic macrocycles have attracted attention as potential therapeutics possessing cell permeability, stability, and easy-to-control variability. Here, we show that enzymes from the patellamide biosynthetic pathway can be harnessed to make macrocycles that are hybrids of amino acids and a variety of manmade chemical building blocks, including aryl rings, polyethers, and alkyl chains. We have made macrocycles with only three amino acids, one of which can be converted to a thiazoline or a thiazole ring. We report the synthesis of 18?peptide hybrid macrocycles, nine of which have been isolated and fully characterized.

SUBMITTER: Oueis E

PROVIDER: S-EPMC5288752 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Synthesis of Hybrid Cyclopeptides through Enzymatic Macrocyclization.

Oueis Emilia E Nardone Brunello B Jaspars Marcel M Westwood Nicholas J NJ Naismith James H JH

ChemistryOpen 20161213 1

Natural products comprise a diverse array of molecules, many of which are biologically active. Most natural products are derived from combinations of polyketides, peptides, sugars, and fatty-acid building blocks. Peptidic macrocycles have attracted attention as potential therapeutics possessing cell permeability, stability, and easy-to-control variability. Here, we show that enzymes from the patellamide biosynthetic pathway can be harnessed to make macrocycles that are hybrids of amino acids and ...[more]

PMID: 28168143

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