A Mechanism-Based Sphingosine-1-phosphate Lyase Inhibitor

J Org Chem. 2020 Jan 17;85(2):419-429. doi: 10.1021/acs.joc.9b02420. Epub 2020 Jan 3.

Abstract

The synthesis of a series of vinylated analogues of sphingosine-1-phosphate together with their unambiguous configurational assignment by VCD methods is reported. Among them, compound RBM10-8 can irreversibly inhibit human sphingosine-1-phosphate lyase (hS1PL) while behaving also as an enzyme substrate. These findings, together with the postulated mechanism for S1PL activity, reinforce the role of RBM10-8 as a new mechanism-based hS1PL inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde-Lyases / antagonists & inhibitors*
  • Aldehyde-Lyases / chemistry
  • Amino Acid Sequence
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Molecular Structure
  • Stereoisomerism

Substances

  • Enzyme Inhibitors
  • Aldehyde-Lyases
  • sphingosine 1-phosphate lyase (aldolase)