Inosine complexes

Inosine complexed with 4-(acetylamino)ben2oic acid and 1-(dimethylamino)-2-propano1 (1 3 3) nolecular formula = CjgHj2N4O5-SCgH CAS Registry Number = [36703-88-5],... 

The formation rate constant for the nickel(Il)-inosine complex... 

Inosine 5 -Monophosphate Dehydrogenase. A series of 21 known inosine 5 -monophosphate dehydrogenase (IMPDH) inhibitors was used to validate a virtual screening protocol. By application of a molecular weight filter (80 < MW < 400), 3425 compounds were extracted from an in-house reagent inventory system. Docking of these compounds into a substrate-IMPDH complex 3D structure was performed with the program FlexX three... 

Adenosine deaminase (ADA) is an amino hydrolase that catalyzes the deamination of adenosine and 2 -deoxyadenosine to inosine and 2 -deoxyinosine, respectively. High activity of ADA is seen in thymus and other lymphoid tissues. ADA has been shown in many different physical forms. A small form of the enzyme predominates in the spleen, stomach, and red blood cells, whereas the large form predominates in the kidney, liver, and skin fibroblasts. The small form of the catalytic subunit can be converted to the large form by complexing with a protein termed binding protein or complexing protein. 

In acidic aqueous solution the complexation of the chloroaqua derivatives of cis- and trans-DDP involves substitution of the aqua ligand with the nucleobase [15]. The trans derivative reacts 10 times faster than the cis isomer with inosine at pH 3, in line with the trans-effect Cl" > NH3. It has been shown that trans- [PtCl(NH3)2(H20)]+ behaves like a mono-... 

Far less data are available from other diaqua Pt(II) compounds. Comparison of the diaqua derivatives of cis- and trans-DDP has shown that their complexation with inosine derivatives is mechanistically similar, but the rate parameters for various steps show considerable differences [40,41], For example, for isomeric [Pt(NH3)2(H20)2]2+ ions kx cis) = 10 k trans), whereas for the [Pt(0H)(NH3)2(H20)]+ ions the difference is k cis) 6 kyitrans) in the formation of 1 1 complexes. The ability of isomeric 1 1 complexes to bind the second nucleobase is, however, very similar in both cases, also by taking proton transfer formally from inosine... 

Products of substitution of inosine and guanosine 5 -monophosphate for chloride or for water on ternary aminocarboxylate complexes such as [Pd(mida)(D20)], where mida = IV-methyliminodiacetate, or [Pd2(hdta)Cl2]2-, where hdta = 1,6-hexanediamine-A(7V,./V,./V,-tetraace-tate, is subject to mechanistic controls in terms of number of coordinated donor atoms and pendant groups and of the length of the chain joining the functional groups in the bis-iminodiacetate ligands. These factors determine the nature and stereochemistry of intermediates and the relative amounts of mono- and bi-nuclear products (253). 

Human type II inosine monophosphate dehydrogenase catalyses NAD-dependent conversion of inosine monophosphate (IMP) into xanthosine monophosphate (XMP) measurements of the primary kinetic isotope effect using [ H]IMP suggest that both substrates (IMP and NAD) can dissociate from the enzyme-substrate complex therefore, the kinetic mechanism is not ordered. NMR studies indicate hydride transfer to the B or pro-S face of the nicotinamide ring of NAD, while kinetic studies suggest... 

All muscarinic receptors are members of the seven transmembrane domain, G protein-coupled receptors, and they are structurally and functionally unrelated to nicotinic ACh receptors. Activation of muscarinic receptors by an agonist triggers the release of an intracellular G-protein complex that can specifically activate one or more signal transduction pathways. Fortunately, the cellular responses elicited by odd- versus even-numbered receptor subtypes can be conveniently distinguished. Activation of Ml, M3, and M5 receptors produces an inosine triphosphate (IP3) mediated release of intracellular calcium, the release of diacylglyc-erol (which can activate protein kinase C), and stimulation of adenylyl cyclase. These receptors are primarily responsible for activating calcium-dependent responses, such as secretion by glands and the contraction of smooth muscle. 

Crystallographic analysis of a number of PNP inhibitor complexes revealed significant displacement of the inhibitors. These displacements appear to be the result of close contacts between the inhibitor and the ion in the phosphate binding site. Sulfate ions occupy the phosphate site in PNP crystals as they are grown from ammonium sulfate solution. These inhibitors were more potent when the binding was measured in 1 mMphosphate solution rather than in 50 mMphosphate. Kinetic studies showed that these inhibitors were competitive not only with inosine but also with phosphate, in keeping with the above observation. 

Purine nucleotides are degraded by a pathway in which they lose their phosphate through the action of 5 -nucleotidase (Fig. 22-45). Adenylate yields adenosine, which is deaminated to inosine by adenosine deaminase, and inosine is hydrolyzed to hypoxanthine (its purine base) and D-ribose. Hypoxanthine is oxidized successively to xanthine and then uric acid by xanthine oxidase, a flavoenzyme with an atom of molybdenum and four iron-sulfur centers in its prosthetic group. Molecular oxygen is the electron acceptor in this complex reaction. 

A number of zinc and cadmium complexes of adenine (82),554,555 adenine N-oxide,556 guanine,557 inosine,558 cytidine559 and other nucleosides560 have been studied. The structure of (9-methyladenine)ZnCl2 is polymeric each zinc ion is tetrahedrally coordinated to two chlorine atoms (Zn—Cl = 2.22 A), and to N-l and N-7 of neighbouring adenine moieties (Zn— N = 2.05A).561 A structural study of the related cadmium complex, CdCl2(DMSO)L (L = 9-methyladenine), has shown the complex to form a one-dimensional polymer. 2... 

The inosine and hypoxanthine were separated by reversed phase high performance liquid chromatography and the amount of hypoxanthine produced was related to the phosphate concentration. Quantitation of the hypoxanthine peak was found to be linear with orthophosphate up to about 30mg L A detection limit of 0.75mg L 1 could be obtained after dialysis of the commercial enzyme. Interference studies showed that the enzymatic assay unlike the colorimetric molybdate blue technique was essentially unaffected by complex matrices such as polyphosphates and phosphoesters. 

This contribution complements an earlier review (11) which summarized our NMR research on synthetic DNA s and RNA s with alternating inosine-cytidine and guanosine-cytidine polynucleotides and the structure and dynamics of ethidium-nucleic acid complexes. 

Table 3. Weighted Relative Rates for Reaction of Complexes (NH3)2Pt11 with Inosine N(7) at pH 7.4 at Plasma and Nuclear Chloride-Ion Concentrations...

However, because of the slowness of Ptn conversions, the various (NH3)2Ptn species may not be at equilibrium with ambient 4 mM chloride in the cell nucleus. The (NH3)2Ptn species may be more nearly in equilibrium with the ambient 104 mM chloride of the blood plasma, where the administered drug has circulated. For conversion from administered dichloro to diaqua complexes in acidic solutions the successive half lives at 45 °C are 1.0 and 0.8 h for cis and 0.18 and 48 h for trans isomers [3], These times agree with the well-documented trans-activating order Cl > NH3 > H20. Therefore, we have performed a similar analysis of the reaction rate with inosine N(7) assuming that the (NH3)2Ptn species are in equilibrium with the blood plasma and the results appear under the columns labeled 104 mu in Table 3. At 104 mM CP, the total reactivities of all cA-species are 1/3, and those of all trans-species 2/3 those at 4 mM. 

Considering the greater basicity of the N(l) site over the N(7) site in purine bases, the N(7) —> N(l) migration of Pt may be anticipated. In fact, this type of isomerization has been observed in Ptn(dien) (dien = diethylene-triamine) complexes of inosine [32] and adenosine [33], Both isomerization reactions have been proposed to follow similar mechanism, i. e., the change... 

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