α,β-Methyleneadenosine 5'-triphosphate (sodium salt)

α,β-Methyleneadenosine 5’-triphosphate (αβ-methylene ATP) is a phosphonic analog of ATP that is characterized by the replacement of the bridging oxygen atom between the α- and β-phosphate groups with methylene. It is an agonist of P2X purinoceptors P2X1 and P2X3 (EC50 = ~1 µM) and is ~1,000-fold less potent at P2X2, P2X receptors 4-7, and P2Y receptors. [1][2][3][4] Persistent activation of purinoceptors results in desensitization, resulting in an antagonist-like effect of αβ-methylene ATP. [5] αβ-methylene ATP is used as a stable analog of ATP to study the interaction of ATP with kinases and other proteins. [6][7] It weakly binds and inhibits adenylate cyclase in a calcium-dependent manner (Ki= ~0.5 mM). [8][9]

Reference:
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[2]. Coddou, C., Yan, Z., Obsil, T., et al. Activation and regulation of purinergic P2X receptor channels. Pharmacological Reviews 63(3), 641-683 (2011).
[3]. Helms, N., Kowalski, M., Illes, P., et al. Agonist antagonist interactions at the rapidly desensitizing P2X3 receptor. PLoS One 8(11), 1-11 (2013).
[4]. Abbracchio, M.P., Burnstock, G., Boeynaems, J.M., et al. International Union of Pharmacology LVIII: Update on the P2Y G protein-coupled nucleotide receptors: From molecular mechanisms and pathophysiology to therapy. Pharmacological Reviews 58(3), 281-341 (2006).
[5]. Dunn, P.M. Fertility: Purinergic receptors and the male contraceptive pill. Current Biology 10(8), R305-R307 (2000).
[6]. Gibson, K.J., Schubert, K.R., and Switzer, R.L. Binding of the substrates and the allosteric inhibitor adenosine 5'-diphosphate to phosphoribosylpyrophosphate synthetase from Salmonella typhimurium. The Journal of Biological Chemisty 257(5), 2391-2396 (1982).
[7]. Steegborn, C., Litvin, T.N., Levin, L.R., et al. Bicarbonate activation of adenylyl cyclase via promotion of catalytic active site closure and metal recruitment. Nature Structural & Molecular Biology 12(1), 32-37 (2005).
[8]. Krug, F., Parikh, I., Illiano, G., et al. αβ-Methylene-adenosine 5'-triphosphate. A competitive inhibitor of adenylate cyclase in fat and liver cell membranes. The Journal of Biological Chemisty 248(4), 1203-1206 (1973).
[9]. Dessauer, C.W., Scully, T.T., and Gilman, A.G. Interactions of forskolin and ATP with the cytosolic domains of mammalian adenylyl cyclase. The Journal of Biological Chemisty 272(35), 22272-22277 (1997).