Adenosine triphosphate analogs

Reduction of l,10-phenanthroline-2-aldehyde to 1,10-phenanthroline-2-carbinol is efficiently accomplished by a dihydronicotinamide derivative in acetonitrile solution catalyzed by zinc ions. This was the first example of the reduction of an aldehyde by a NADH analog in a nonenzymic system. It also supports the catalytic function of the metal ion in the enzymic system.359 l,10-Phenanthroline-2-carbinol, obtained by sodium borohydride reduction of 2-carbomethoxy-1,10-phenanthroline, is phosphorylated by adenosine triphosphate in the presence of zinc ions.360... 

Kinetic studies of the nucleotide analogs, y-phenylpropyl di- and triphosphate, have been undertaken to define the role of the adenosine residue in the chemical and enzymic reactions of adenosine triphosphate. A catalytic function associated with binding of metal ions at the adenine nitrogens has been ascribed to the adenosine moiety in phosphate transfer reactions in which adenosine di- or triphosphates function as the phosphate source109-"2. The pH-rate profile (Fig. 6) for the hydrolysis of -y-phenylpropyl diphosphate... 

Vidarabine [vye DARE a been] arabinofuranosyl adenine, ara-A, adenine arabinoside) is one of the most effective of the nucleoside analogs and is also the least toxic. However, it has been supplanted clinically by acyclovir, which is more efficacious and safe. Although vidarabine is active against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), its use is limited to treatment of immunocompromised patients with herpes simplex keratitis or encephalitis, or VZV infections. Vidarabine, an adenosine analog, is converted in the cell to its 5 -triphosphate analog (ara-ATP), which is postulated to inhibit viral DNA synthesis. Some resistant herpes virus... 

The simplest use of manganese is as part of a metal cofactor such as manganese(II) adenosine triphosphate, [Mn(II)ATP2-]. The metal complex is usually found as the bidentate [Mn(II)0,7-ATP2 ] (3, 4) as illustrated in Figure 1. Enzyme specificity for Mg(II), Mn(II), or Ca(II) ATP complexes is dependent on a variety of factors however, once selected, each metal apparently functions in an analogous manner. The metal ion serves two main purposes. First, based on the coordination geometry... 

The enzyme 5-oxo-L-prolinase, which catalyses the conversion of 5-oxo-L-proline to L-glutamate coupled to the consumption of adenosine triphosphate (ATP) (Figure 36.39), was shown by Williamson and Meister to act also on a synthetic substrate, L-2-oxothiazolidine -carboxylate, which is an analog of 5-oxoproline with the 4-methylene group replaced by sulfur. 

Liu, X., Zhang, X.-R., and Blackburn, G.M., Synthesis of three novel supercharged p.y-mclhylcnc analogs of adenosine triphosphate, J. Chem. Soc., Chem. Commun., 87, 1997. 

Also present in the first test tnbe is a synthetic analog of adenosine triphosphate in which both the T and 3 hydroxyl gronps have been replaced by hydrogens. This componnd is called 2, 3 -dideoxyadenosine triphosphate (ddATP). Similarly, ddTTP is added to the second tube, ddGTP to the third, and ddCTP to the fourth. Each tube also contains a primer. The primer is a short section of the complementary DNA strand, which has been labeled with a radioactive isotope of phosphorus ( P) that emits a particles. When the electrophoresis gel is examined at the end of the experiment, the positions of the DNAs formed by chain extension of the primer are located by detecting their a emission by a techniqne called autoradiography. 

An ADA-resistant purine analog, cladribine (2-chlorodeoxyadenosine 2-CdA) has demonstrated potent activity in hairy cell leukemia, CLL, and low-grade lymphomas. After intracellular phosphorylation by deoxycytidine kinase and conversion to cladribine triphosphate, it is incorporated into DNA. It produces DNA strand breaks and depletion of NAD and adenosine triphosphate (ATP), as well as apoptosis, and is a potent inhibitor of ribonucleotide reductase. The drug does not require cell division to be cytotoxic. Resistance is associated with loss of the activating enzyme, deoxycytidine kinase, or escape of ribonucleotide reductase from inhibition. 

The actin-myosin muscle system provides the performance target for electroactive polymer actuators [3, 4]. The process is driven chemically by the energy change from hydrolysis of the polyphosphate bond as ATP (adenosine triphosphate) binds to myosin and is converted to ADP (adenosine diphosphate) and phosphate. A simple chemical analogy suggests that muscle-like gels should be feasible but it is now clear that the task is much harder than it seems. 

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