title: The chemical synthesis of metabolically stabilized 2-OMe-LPA analogues and preliminary studies of their inhibitory activity toward autotaxin.
abstract: The chemical synthesis of five new metabolically stabilized 2-OMe-LPA analogues (1a-e) possessing different fatty acid residues has been performed by phosphorylation of corresponding 1-O-acyl-2-OMe-glycerols which were prepared by multistep process from racemic glycidol. The now analogues were subjected to biological characterization as autotaxin inhibitors using the FRET-based, synthetic ATX substrate FS-3. Among tested compounds 1-O-oleoyl-2-OMe-LPA (1e) appeared to be the most potent, showing ATX inhibitory activity similar to that of unmodified 1-O-oleoyl-LPA. Parallel testing showed, that similar trend was also observed for corresponding 1-O-acyl-2-OMe-phosphorothioates (2a-e, synthesized as described by us previously). 1-O-oleoyl-2-OMe-LPA (1e) was found to be resistant toward alkaline phosphatase as opposed to unmodified 1-O-oleoyl-LPA.
authors.affiliation: Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Technical University of Lodz, Lodz, Poland. edarmach@wp.pl
authors.forename: Edyta
authors.initials: E
authors.lastname: Gendaszewska-Darmach
authors.forename: Edyta
authors.initials: E
authors.lastname: Laska
authors.forename: Przemysław
authors.initials: P
authors.lastname: Rytczak
authors.forename: Andrzej
authors.initials: A
authors.lastname: Okruszek
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008246:Lysophospholipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008745:Methylation; D015394:Molecular Structure; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors; D000099189:Lysophospholipase D
chemical_list: D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D000099189:Lysophospholipase D; C574955:1-O-oleoyl-2-OMe-lysophosphatidic acid