Synthesis of Hybrid Cyclopeptides through Enzymatic Macrocyclization.
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.
School of Chemsitry University of St Andrews BSRC, North Haugh St Andrews KY16 9ST UK.
Emilia
E
Oueis
School of Chemsitry University of St Andrews BSRC, North Haugh St Andrews KY16 9ST UK.
Brunello
B
Nardone
Marine Biodiscovery Centre Department of Chemistry University of Aberdeen Old Aberdeen AB24 3UE UK.
Marcel
0000-0002-2426-6028
M
Jaspars
School of Chemsitry University of St Andrews BSRC, North Haugh St Andrews KY16 9ST UK.
Nicholas J
0000-0003-0630-0138
NJ
Westwood
School of Chemsitry University of St Andrews BSRC, North Haugh St Andrews KY16 9ST UK; State Key Laboratory of Biotherapy Sichuan University P. R. China.
James H
0000-0001-6744-5061
JH
Naismith
biotransformation; cyanobactin; hybrid macrocycles; macrocyclization; peptides