Synthesis of a hydrolytically stable, fluorescent-labeled ATP analog as a tool for probing adenylyl cyclases

Thomas Emmrich; Ali El-Tayeb; Hesham Taha; Roland Seifert; Christa E Müller; Andreas Link

doi:10.1016/j.bmcl.2009.10.125

Synthesis of a hydrolytically stable, fluorescent-labeled ATP analog as a tool for probing adenylyl cyclases

Bioorg Med Chem Lett. 2010 Jan 1;20(1):232-5. doi: 10.1016/j.bmcl.2009.10.125. Epub 2009 Oct 30.

Authors

Thomas Emmrich¹, Ali El-Tayeb, Hesham Taha, Roland Seifert, Christa E Müller, Andreas Link

Affiliation

¹ Institute of Pharmacy, Ernst-Moritz-Arndt-University, Friedrich-Ludwig-Jahn-Strasse 17, D-17487 Greifswald, Germany.

PMID: 19914832
DOI: 10.1016/j.bmcl.2009.10.125

Abstract

(2R,3S,4R,5R)-5-(6-Amino-9H-purin-9-yl)-3-hydroxy-4-[2-(methylamino)benzamido]tetrahydrofuran-2-yl-methoxy[(hydroxy)phosphoryloxy][(hydroxy)phosphoryl]dichloromethylphosphonic acid was synthesized as a chemically and metabolically stable analog of ATP substituted with a fluorescent methylanthranoyl (MANT) residue. The compound is intended for studying the binding site and function of adenylyl cyclases (ACs), which was exemplified by studying its interaction with Bacillus anthracis edema factor (EF) AC exotoxin.

MeSH terms

Adenosine Triphosphate / analogs & derivatives*
Adenosine Triphosphate / chemical synthesis
Adenosine Triphosphate / pharmacology
Adenylyl Cyclases / chemistry*
Adenylyl Cyclases / metabolism
Bacillus anthracis / enzymology
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Fluorescent Dyes / chemistry*
Hydrogen Bonding
Organophosphorus Compounds / chemical synthesis*
Organophosphorus Compounds / chemistry
Organophosphorus Compounds / pharmacology

Substances

Enzyme Inhibitors
Fluorescent Dyes
Organophosphorus Compounds
(dichloromethyl)phosphonic acid
Adenosine Triphosphate
Adenylyl Cyclases