Jacobson - 2019

Molecular Recognition Section, Laboratory of Bioorganic Chemistry
NIDDK
Mentor Name
Kenneth A. Jacobson, Ph.D.
Mentor Email
Mentor Telephone
301-496-9024
Laboratory And Project Description

We study the structure and pharmacology of receptors and discover drugs that act as agonists or antagonists of G protein-coupled receptors (GPCRs). Our current focus is on receptors for purines, encompassing both adenosine receptors and P2 receptors, which are activated by ATP, UTP and other extracellular nucleotides. We have taken an interdisciplinary approach to studying the chemical and biological aspects of these receptors using convergent modeling, mutagenesis and structure-based approaches. Detailed information about the three-dimensional structure of this receptor family aids in the design and chemical synthesis of novel ligands. We collaborate on the X-ray crystallographic structures of various purine (adenosine and P2Y) receptors with Ray Stevens of the University of Southern California. Two agonists of the A3 adenosine receptor (both discovered in our lab) have progressed to advanced clinical trials for the treatment of autoimmune inflammatory diseases, liver diseases and cancer. We are currently designing adenosine receptor agonists for use in treating chronic neuropathic pain, an unmet medical need, and P2Y receptor antagonists for inflammation.

Dr. Jacobson’s NIDDK website:
https://www.niddk.nih.gov/about-niddk/staff-directory/biography/jacobso…

Interns may provide support for research in the following areas:

  • Organic synthesis and characterization of new nucleoside analogues as agonists of the adenosine receptors, aimed at expanding the structure activity relationship.
  • Organic synthesis and characterization of novel heterocyclic derivatives as antagonists of several subtypes of P2Y receptors.
  • Development and optimization of fluorescent assays for receptor binding in whole cells.