52977-37-4Relevant academic research and scientific papers
Kinetics and docking studies on the effect of chemical modification of NADH for redox reactions with dehydrogenases
Ma, Hongjing,Zhang, Songping,Su, Zhiguo,Wang, Ping
, p. 111 - 118 (2012)
Cofactor analogs promise important applications in biosynthesis. The effect of chemical modification on the reactivity of NADH for redox reactions catalyzed by dehydrogenases was examined in this work. Compared with the native NADH, kinetics and molecular docking studies with 8-(6-aminohexyl)-amino-NADH showed that its binding with alcohol dehydrogenase (ADH) was not much affected or even enhanced by a factor of 4.9-fold with lactate dehydrogenase (LDH), but complicated the binding of substrates to the enzymes. For ADH, the Michaelis constant for acetaldehyde decreased from 0.47 to 0.048 mM, while that of sodium pyruvate with LDH increased to 0.81 from 0.18 mM. On the other hand, the modified coenzyme showed a 19.3-fold decrease in turnover number (k cat) with ADH, while a slight increase with LDH. Molecular docking analysis showed that the hexanediamine arm on the modified coenzyme generated an extra hydrogen bond at the active site of ADH, as well as additional hydrophobic interactions with both ADH and LDH. It appeared that the apparently decreased reactivity of modified cofactor with ADH was caused mainly by the enhanced stability of ternary coenzyme-enzyme-substrate complex, while in the case of LDH, the reduced substrate binding as a result of the chemical modification of NADH led to a slight increase in the overall reaction reactivity.
Synthesis of fluorinated NAD as a soluble coenzyme for enzymatic chemistry in fluorous solvents and carbon dioxide
Panza, Janice L,Russell, Alan J,Beckman, Eric J
, p. 4091 - 4104 (2002)
The synthesis of the coenzyme nicatinamide adenine dinucleotide (NAD) with an covalently attached fluorinated polymer is reported. The fluorinated NAD (FNAD) was rendered soluble in both fluorous solvents and liquid carbon dioxide due to the attachment of a perfluoropolyether. The enzyme horse liver alcohol dehydrogenase (HLADH) was active in catalyzing oxidation/reduction reactions using FNAD as a soluble coenzyme in a fluorous solvent, methoxynonafluorobutane (HFE), and liquid carbon dioxide. In both solvents, the activity of HLADH using FNAD was greater than the same molar amount of unmodified (insoluble) NAD, indicating that a soluble coenzyme results in more efficient reactions.
2′-deoxy cyclic adenosine 5′-diphosphate ribose derivatives: Importance of the 2′-hydroxyl motif for the antagonistic activity of 8-substituted cADPR derivatives
Zhang, Bo,Wagner, Gerd K.,Weber, Karin,Garnham, Clive,Morgan, Anthony J.,Galione, Antony,Guse, Andreas H.,Potter, Barry V. L.
, p. 1623 - 1636 (2008/09/20)
The structural features needed for antagonism at the cyclic ADP-ribose (cADPR) receptor are unclear. Chemoenzymatic syntheses of novel 8-substituted 2′-deoxy-cADPR analogues, including 8-bromo-2′-deoxy-cADPR 7, 8-amino-2′-deoxy-cADPR 8, 8-O-methyl-2′-deoxy-cADPR 9, 8-phenyl-2′-deoxy-cADPR 10 and its ribose counterpart 8-phenyl-cADPR 5 are reported, including improved syntheses of established antagonists 8-amino-cADPR 2 and 8-bromo-cADPR 3. Aplysia californica ADP-ribosyl cyclase tolerates even the bulky 8-phenyl-nicotinamide adenine 5′-dinucleotide as a substrate. Structure-activity relationships of 8-substituted cADPR analogues in both Jurkat T-lymphocytes and sea urchin egg homogenate (SUH) were investigated. 2′-OH Deletion decreased antagonistic activity (at least for the 8-amino series), showing it to be an important motif. Some 8-substituted 2′-deoxy analogues showed agonist activity at higher concentrations, among which 8-bromo-2′-deoxy-cADPR 7 was, unexpectedly, a weak but almost full agonist in SUH and was membrane-permeant in whole eggs. Classical antagonists 2 and 3 also showed previously unobserved agonist activity at higher concentrations in both systems. The 2′-OH group, without effect on the Ca 2+-mobilizing ability of cADPR itself, is an important motif for the antagonistic activities of 8-substituted cADPR analogues.
SYNTHESIS OF CONJUGATES OF 11α-HYDROXYPROGESTERONE WITH β-NICOTINAMIDE ADENINE DINUCLEOTIDE (β-NAD) AND ADENOSINE TRIPHOSPHATE (ATP)
Kirk, David N.,Miller, Barry W.
, p. 2983 - 2992 (2007/10/02)
Conjugates of 11α-hydroxyprogesterone with adenosine triphosphate and nicotinamide adenine dinucleotide have been prepared in which the steroid is attached to the nucleotides via bridges from C-11 to the terminal phosphate and C-8 positions ATP, and to the N-6 and C-8 positions on the adenine ring of NAD.Preliminary evaluation of the bioluminescence of these conjugates is reported.
