Adenosine analogs with covalently attached lipids have enhanced potency at A1-adenosine receptors

Kenneth A. Jacobson, Jeffrey Zimmet, Richard Schulick, Suzanne Barone, John W. Daly, Kenneth L. Kirk

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Chemically functionalized congeners of N6-phenyladenosine and 1,3-dipropyl-8-phenylxanthine have been covalently coupled to fatty acids, diglycerides, and a phospholipid. The lipid-drug conjugates inhibit R-[3H]-phenylisopropyladenosine binding to A1-adenosine receptors in rat cerebral cortex membranes. A xanthine-phosphatidylethanolamine conjugate bound with a Ki value of 19 nM. Various xanthine esters of low potency are potential prodrugs. Amides of an adenosine amine congener (ADAC) with 18-carbon fatty acids exhibited Ki values at A1-adenosine receptors of 70 pM, representing a 130-fold enhancement over the affinity of the corresponding acetyl amide. The very high affinity of adenosine-lipid conjugates may be due to stabilization of these adducts in the phospholipid microenvironment of the receptor protein.

Original languageEnglish (US)
Pages (from-to)97-102
Number of pages6
JournalFEBS Letters
Issue number1-2
StatePublished - Dec 10 1987
Externally publishedYes


  • Adenosine derivative
  • Adenosine receptor
  • Lipid
  • Lipid-drug conjugate
  • Prodrug
  • Xanthine

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


Dive into the research topics of 'Adenosine analogs with covalently attached lipids have enhanced potency at A1-adenosine receptors'. Together they form a unique fingerprint.

Cite this