title: Suramin analogs, divalent cations and ATP gamma S as inhibitors of ecto-ATPase.
abstract: Ecto-nucleotidases are plasma membrane-bound enzymes that sequentially dephosphorylate extracellular nucleotides such as ATP. This breakdown of ATP and other nucleotides obscures the characterization and classification of P2 (nucleotide) receptors. We therefore studied suramin and several of its analogs, divalent cations and ATP gamma S for their ability to inhibit ecto-ATPase in human blood cells. Suramin itself and Ni2+ were the more potent, non-competitive inhibitors with micromolar affinity. ATP gamma S also displayed micromolar affinity and inhibited ecto-ATPase competitively. The data obtained with the divalent cations demonstrate that coordination of the phosphate chain but not the N7 of the adenine ring is required for the breakdown of ATP by ecto-ATPase. Divalent cations that coordinate both the phosphate chain and N7 inhibit ecto-ATPase in a non-competitive manner.
authors.affiliation: Leiden/Amsterdam Center for Drug Research, Division of Medicinal Chemistry.
authors.forename: M W
authors.initials: MW
authors.lastname: Beukers
authors.forename: C J
authors.initials: CJ
authors.lastname: Kerkhof
authors.forename: M A
authors.initials: MA
authors.lastname: van Rhee
authors.forename: U
authors.initials: U
authors.lastname: Ardanuy
authors.forename: C
authors.initials: C
authors.lastname: Gurgel
authors.forename: H
authors.initials: H
authors.lastname: Widjaja
authors.forename: P
authors.initials: P
authors.lastname: Nickel
authors.forename: A P
authors.initials: AP
authors.lastname: IJzerman
authors.forename: W
authors.initials: W
authors.lastname: Soudijn
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000345:Affinity Labels / Q000494:pharmacology*; D001773:Blood Cells / Q000201:enzymology; D002413:Cations, Divalent / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D006801:Humans; D008433:Mathematics; D008628:Mercury / Q000494:pharmacology; D008670:Metals / Q000494:pharmacology*; D018048:Receptors, Purinergic P2 / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013498:Suramin / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000345:Affinity Labels; D002413:Cations, Divalent; D008670:Metals; D018048:Receptors, Purinergic P2; C022571:adenosine 5'-O-(3-thiotriphosphate); D013498:Suramin; D003300:Copper; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D008628:Mercury