Synthesis of dansyl labeled sphingosine kinase 1 inhibitor

Chem Phys Lipids. 2018 Sep:215:29-33. doi: 10.1016/j.chemphyslip.2018.07.005. Epub 2018 Jul 22.

Abstract

PF-543 is a non-sphingosine analogue with inhibitory effect against SK1, based on a Ki of 4.3 nM and 130-fold selectivity for SK1 over SK2. Since the development of PF-543, animal studies demonstrated its valuable role in multiple sclerosis, myocardial infarction, and colorectal cancer. We synthesized labeled PF-543 for biochemical studies involving SK1. Overall, the 8-step synthetic route used 3,5-dimethylphenol as the starting material. A docking study of SK1 and SK1 inhibitory activity confirmed the structural similarity between the synthetic dansyl-PF-543 and PF-543. We also provide fluorescence spectra of dansyl-PF-543.

Keywords: Cancer; Dansyl; Inhibitor; Label; PF-543; Sphingosine kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Fluorescent Dyes / chemistry*
  • Methanol
  • Molecular Docking Simulation
  • Molecular Structure
  • Phosphatidylcholines / chemistry*
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
  • Protein Binding
  • Protein Kinase Inhibitors / chemistry*
  • Pyrrolidines / chemistry*
  • Spectrometry, Fluorescence
  • Structure-Activity Relationship
  • Sulfones / chemistry*
  • Xylenes / chemistry

Substances

  • 1-myristoyl-2-(12-((5-dimethylamino-1-naphthalenesulfonyl)amino)dodecanoyl)-sn-glycero-3-phosphocholine
  • Fluorescent Dyes
  • PF-543
  • Phosphatidylcholines
  • Protein Kinase Inhibitors
  • Pyrrolidines
  • Sulfones
  • Xylenes
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase
  • 3,5-xylenol
  • Methanol