Anion Receptors for the Discrimination of ATP and ADP in Biological Media

Abstract

The design and synthesis of molecular receptors for the selective binding of nucleoside phosphate anions (e. g. ATP, ADP, GTP, GDP, UDP) in aqueous media at physiological pH is a valuable research endeavour, which could lead to new sensing tools for biomedical and drug discovery research. However, this target is very challenging due to similarities in anion size, structure and charge. This Minireview provides an account of the development of receptors capable of discriminating between ATP and ADP, and their utilisation in biological sensing applications. Particular focus is given to the application of receptors for the determination of ATP or ADP concentrations in biological media, tracking ATP levels (or the ATP/ADP ratio) in cells using fluorescence microscopy, or real‐time monitoring of enzyme reactions involving ATP and ADP in vitro.

Sterically demanding macrocyclic Eu(iii) complexes for selective recognition of phosphate and real-time monitoring of enzymatically generated adenosine monophosphate

“…Crucially, the sensing selectivity of the receptors follows the order AMP > ADP > ATP, which is opposite to that observed for most nucleoside phosphate receptors 6–8 where the binding is governed predominantly by electrostatic interactions and thus favours ATP and ADP over AMP. We have previously shown that ATP and ADP prefer to adopt a bidentate binding mode in more conformationally flexible macrocyclic Ln( iii ) receptors.…”

“…5 Adenosine monophosphate (AMP) represents a valuable yet very difficult target for supramolecular detection because of its similarities with the more negatively charged anions, ATP and ADP. 6–8…”

“…5 Adenosine monophosphate (AMP) represents a valuable yet very difficult target for supramolecular detection because of its similarities with the more negatively charged anions, ATP and ADP. [6][7][8] Inorganic phosphate plays important roles in the functions of muscles and nerves and skeletal mineralisation. The level of phosphate in human blood is maintained within a relatively narrow range (0.8-1.45 mM), 9 similar to lactate levels (0.5-1.0 mM) and substantially lower than bicarbonate (23-29 mM) and chloride (98-115 mM).…”

“…[27][28][29] Indeed, most reported nucleoside phosphate receptors exhibit a selectivity prole that is governed predominantly by electrostatic interactions and thus follows the order ATP > ADP > AMP. 6,8,[30][31][32] Such receptors are not suitable for detecting AMP during enzyme reactions, especially in the presence of ATP.…”

Synform Issue 2021/09

“…[1][2][3][4][5] Nucleoside phosphate anions are critical to the maintenance of life and play crucial roles in energy transduction, cellular signalling and membrane trans port. 6,7 We have developed a new class of emissive europium complexes bearing arms that bind selectively to ATP and ADP through a combination of electrostatic and hydrogen bonding interactions. Our lead molecule is capable of realtime anal ysis of kinase enzyme activity by monitoring the production of ADP, thereby providing a convenient luminescence assay for screening of potential kinase inhibitors.…”