Saturation molalities and standard molar enthalpies of solution of 2′-deoxyadenosine·H2O(cr), 2′-deoxycytidine·H2O(cr), 2′-deoxyguanosine·H2O(cr), 2′-deoxyinosine(cr), and 2′-deoxyuridine(cr) in H2O(l)

Tewari, Yadu B.; Gery, Patrick D.; Vaudin, Mark D.; Mighell, A. D.; Klein, Ralph; Goldberg, Robert N.

doi:10.1016/j.jct.2004.09.008

Cited by 7 publications

References 20 publications

(36 reference statements)

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Bisubstrate Inhibitors of Catechol O‐Methyltransferase (COMT): the Crucial Role of the Ribose Structural Unit for Inhibitor Binding Affinity

et al. 2006

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Inhibition of the enzyme catechol O-methyltransferase offers a therapeutic handle to regulate the catabolism of catecholamine neurotransmitters, providing valuable assistance in the treatment of CNS disorders such as Parkinson's disease. A series of ribose-modified bisubstrate inhibitors of COMT featuring 2'-deoxy-, 3'-deoxy-, 2'-aminodeoxy-3'-deoxy-, and 2'-deoxy-3'-aminodeoxyribose-derived central moieties and analogues containing the carbocyclic skeleton of the natural product aristeromycin were synthesized and evaluated to investigate the molecular recognition properties of the ribose binding site in the enzyme. Key synthetic intermediates in the ribose-derived series were obtained by deoxygenative [1,2]-hydride shift rearrangement of adenosine derivatives; highlights in the synthesis of carbocyclic aristeromycin analogues include a diastereoselective cyclopropanation step and nucleobase introduction with a modified Mitsunobu protocol. In vitro biological evaluation and kinetic studies revealed dramatic effects of the ribose modification on binding affinity: 3'-deoxygenation of the ribose gave potent inhibitors (IC50 values in the nanomolar range), which stands in sharp contrast to the remarkable decrease in potency observed for 2'-deoxy derivatives (IC50 values in the micromolar range). Aminodeoxy analogues were only weakly active, whereas the change of the tetrahydrofuran skeleton to a carbocycle unexpectedly led to a complete loss of biological activity. These results confirm that the ribose structural unit of the bisubstrate inhibitors of COMT is a key element of molecular recognition and that modifications thereof are delicate and may lead to surprises.

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Bisubstrate Inhibitors of Catechol O‐Methyltransferase (COMT): the Crucial Role of the Ribose Structural Unit for Inhibitor Binding Affinity

et al. 2006

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The Partial Molar Heat Capacities and Expansions of Inosine, 2′-Deoxyinosine and 2′-Deoxyguanosine in Aqueous Solution at 298.15 K

Hedwig

2009

J Solution Chem

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Volumetric interaction coefficients for some nucleosides in aqueous solution at T=298.15K

Hedwig

Jameson

2013

The Journal of Chemical Thermodynamics

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Saturation molalities and standard molar enthalpies of solution of 2′-deoxyadenosine·H2O(cr), 2′-deoxycytidine·H2O(cr), 2′-deoxyguanosine·H2O(cr), 2′-deoxyinosine(cr), and 2′-deoxyuridine(cr) in H2O(l)

Cited by 7 publications

References 20 publications

Bisubstrate Inhibitors of Catechol O‐Methyltransferase (COMT): the Crucial Role of the Ribose Structural Unit for Inhibitor Binding Affinity

Bisubstrate Inhibitors of Catechol O‐Methyltransferase (COMT): the Crucial Role of the Ribose Structural Unit for Inhibitor Binding Affinity

The Partial Molar Heat Capacities and Expansions of Inosine, 2′-Deoxyinosine and 2′-Deoxyguanosine in Aqueous Solution at 298.15 K

Volumetric interaction coefficients for some nucleosides in aqueous solution at T=298.15K

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