title: Nonribosomal assembly of natural lipocyclocarbamate lipoprotein-associated phospholipase inhibitors.
abstract: EXPANDING OUR KNOWLEDGE: Natural lipocyclocarbamate natural products have provided the inspiration for the first-in-class synthetic phospholipase inhibitor darapladib, currently in phase III clinical trials for the treatment of atherosclerosis. Here, we discuss their biosynthesis by a nonribosomal peptide synthetase.
authors: Department of Chemistry and Chemical Biology and Department of Biochemistry and Biomedical Sciences, M. G. DeGroote Institute for Infectious Disease Research, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8N 3Z5, Canada.
authors: Chad W
authors: CW
authors: Johnston
authors: Rostyslav
authors: R
authors: Zvanych
authors: Nadiya
authors: N
authors: Khyzha
authors: Nathan A
authors: NA
authors: Magarvey
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000037:antagonists & inhibitors*; D050197:Atherosclerosis / Q000188:drug therapy; D001547:Benzaldehydes / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D002219:Carbamates / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D010091:Oximes / Q000737:chemistry; D010453:Peptide Synthases / Q000378:metabolism*; D011551:Pseudomonas fluorescens / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides
chemical_list: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D001547:Benzaldehydes; D001688:Biological Products; D002219:Carbamates; D004791:Enzyme Inhibitors; D010091:Oximes; D010453:Peptide Synthases; C529040:darapladib; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides