A Mechanism-Based Sphingosine-1-phosphate Lyase Inhibitor

  • J Org Chem. 2020 Jan 17;85(2):419-429. doi: 10.1021/acs.joc.9b02420.
Guillem Pons  1 ,  Daniel Riba  1 ,  Mireia Casasampere  1  2 ,  Eduardo Izquierdo  1  2 ,  José-Luís Abad  1 ,  Gemma Fabriàs  1  3 ,  Pilar G Rodríguez Ortega  4 ,  Juan J López-González  4 ,  Manuel Montejo  4 ,  Josefina Casas  1  3 ,  Antonio Delgado  1  2
Affiliations
  • 1. Spanish National Research Council (CSIC), Institute for Advanced Chemistry of Catalonia (IQAC-CSIC) , Research Unit on Bioactive Molecules (RUBAM), Department of Biological Chemistry , Jordi Girona 18-26 , 08034 Barcelona , Spain.
  • 2. University of Barcelona (UB) , Faculty of Pharmacy, Department of Pharmacology, Toxicology and Medicinal Chemistry, Unit of Pharmaceutical Chemistry (Associated Unit to CSIC) , Avda. Joan XXIII s/n , 08028 Barcelona , Spain.
  • 3. Centro de Investigación Biomédica en Red (CIBEREHD) , 28029 Madrid , Spain.
  • 4. University of Jaén , Faculty of Experimental Sciences, Department of Physical and Analytical Chemistry , Campus Las Lagunillas , 23071 Jaén , Spain.
PMID: 31860798 DOI: 10.1021/acs.joc.9b02420
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.

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