Format

Send to

Choose Destination
FEBS Lett. 1987 Dec 10;225(1-2):97-102.

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

Author information

1
Laboratory of Chemistry, NIDDK, Bethesda, MD 20892.

Abstract

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.

PMID:
3691809
PMCID:
PMC4287258
DOI:
10.1016/0014-5793(87)81138-9
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center