Purine ribonucleoside

It is particularly interesting that 6-mercaptopurine ribonucleoside (XXI) [158] is an inhibitor of, but not a substrate for, the kinase [47] but 6-(methylthio)purine ribonucleoside (XXII) [159, 160], resulting from the... 

A -Methyladenosine (XXV) (227, 239, 250], fV-methy 1-2 -deoxyadenosine (XXVI) [57], 3 -amino-V-methyl-3-deoxyadenosine [254], and 6-methoxy-purine ribonucleoside (LII) [63, 234, 241] are all good inhibitors of adenosine deaminase and fV-methyladenosine (XXV) has been used in combination with 9-/3-D-arabinofuranosyladenine (XIX) to increase its activity [255]. A number of 2-substituted A -methyladenosines [61] and 9-substituted adenines (see reference 256 and earlier papers by Schaeffer) are also inhibitors of the enzyme. 

RNA polymerase, and the triphosphates of the purine ribonucleosides, uridine, and cytidine, and otherwise the same conditions, will prime the synthesis of RNA. The amounts of synthetic DNA or RNA are many fold greater than the amount of primer DNA the DNA product is nearly the same in most measurable ways as the primer DNA. The efficiency of the DNA in initiating these syntheses is known as the primer activity of the DNA, and can be affected by alterations of the bases which compose the nucleic acid, and by other factors. 

Additional information <1> (<1>, the deletion mutants rDm-dNKAClO and rDm-dNKAC20 show the same substrate activity pattern as the recombinant wild-type enzyme. Relative phosphorylation of 2 -deoxycytidine and 2-chloro-2 -deoxyadenosine increases with increasing C-terminal truncation. The relative activities of rDm-dNKAClO and rDm-dNKAC20 with deoxyribonucleosides remains largely unchanged, whereas there is a substantial decrease in the phosphorylation of the purine ribonucleosides adenosine and guanosine, as well as of all dideoxyribonucleosides and 3 -azido-2 ,3 -dide-oxythymidine. The relative activities with the pyrimidine ribonucleosides and l-/l-D-arabinofuranosylcytosine and l-/i-D-arabinofuranosylthymine are not affected by the C-terminal deletions [4]) [4]... 

The absence of nitro groups in these substrates is noteworthy. The observed adducts are exclusively stabilized by the electron-withdrawing capacity of the aza groups present in the fused ring system of purine. Accordingly, all ring protons in the adducts are more shielded than the corresponding protons in the substrates. Adducts 19 and 20 can be taken as models for intermediates in nucleophilic aromatic substitution at the C-6 position of purine. Moreover, their formation support the view that a tetrahedral carbon at C-6 is involved in the mechanism of the adenosine deaminase-catalyzed hydrolysis of 6-substituted purine ribonucleosides.43... 

The conversions of inosine to hypoxanthine (Fig. 25-17, step e), of guanosine to guanine (step g), and of other purine ribonucleosides and deoxyribonucleo-sides to free purine bases are catalyzed by purine nucleoside phosphorylase.318 321b Absence of this enzyme also causes a severe immune deficiency which involves the T cells. However, B cell function is not impaired.312 315 322... 

The Suzuki—Miyaura reaction of protected 6-chloropurine and 2-amino-6-chloropurine bases and nucleosides with substituted phenylboronic acids led to the corresponding protected 6-(substituted phenyl)purine derivatives 6—9. Their deprotection yielded a series of substituted 6-phenylpurine bases and nucleosides 10—13. Significant cytostatic activity (IC50 0.25—20 /tmol/ L) in CCRF-CEM, HeLa, and L1210 cell lines was found for several 6-(4-X-substituted phenyl-purine ribonucleosides 12 (X = H, F, Cl, and OR), while the 6-phenylpurine and 2-amino-6-phenylpurine bases 10 and 11, as well as 2-amino-6-phenylpurine ribosides 13, were entirely inactive against these cell lines. 

Of considerable interest in relation to the results of Linschitz Connolly was the subsequent finding of Wolfenden et al. 161) that the photochemical adduct of methanol to purine ribonucleoside is a potent inhibitor of adenosine deaminase, in large part because of its structural resemblance to the presumed transition state intermediate involved in the deaminase reaction. 

Similarly to other purine ribonucleosides, isoguanosine can be brominated with bromine in acetic acid to give 8-bromoisoguanosine (10) bromination in buffered aqueous medium, which has been used in the case of adenosine or guanosine, is not successful due to oxidation. ... 

Purine nucleosides are cleaved by the action of purine nucleoside phosphorylase with the liberation of ribose 1-phosphate (Kl, PI). The enzyme is apparently specific for purines. The material from erythrocytes catalyzes the phosphorolysis of purine but not pyrimidine nucleosides (T6.) Purine phosphorylase activity is found widespread in nature and in many animal tissues (FIO). Friedkin and Kalckar investigated an enzyme capable of cleaving purine deoxynucleosides to the aglycone and deoxy-ribose 1-phosphate. They concluded that the enzyme was identical to that which splits purine ribonucleosides (F8, F9). This enzyme is capable of degrading inosine, xanthosine, and guanosine to forms readily attacked by other enzymes. In so doing, it permits living cells to retain the ribose and deoxyribose moieties. 

The ring structure of the sugar of the purine ribonucleosides was shown by chemical methods to be furanoid by Levene and Tipson. These studies have been adequately reviewed by Tipson. The fact that 2-deoxy-inosine and 2-deoxyguanosine do not affect the conductivity of boric acid solutions indicates the absence of a m-1,2-glycol system and, coupled with the anhydronucleoside formation mentioned below, provides evidence that the purine 2-deoxyribonucleosides are also in the furanoid form. 

The structure of purine ribonucleosides has recently been studied by proton-magnetic resonance, and the conformation of the D-ribofuranosyl residue in adenosine and inosine has been determined by an analysis of proton-magnetic resonance data C-2 is considered to be out of the plane defined either by C-1, 0, and C-4 or by C-1, 0, C-3, and C-4 and is pointing on the same side as the C-4—C-5 bond. A similar study of deoxy-ribonucleosides suggests that the ring-oxygen atom and, possibly, C-1 of this sugar moiety may be twisted out of the plane of the five-membered... 

Small amounts of purine ribonucleosides and deoxyribo -nucleosides can be prepared enzymically. Two types of enzyme have been found that catalyze the synthesis of nucleosides. The first are the nucleoside phos-phorylases, which catalyze the reaction of purines and D-ribosyl phosphate or 2-deoxy- D-ribosyl phosphate as follows. 

Although procyclic forms of T. brucei gambiense are incapable of de novo synthesis, the last two enzymes of the pathway are present since the intermediate 5-amino-imidazolo-4-carboxamide ribosylphosphate (AICAR) will maintain viability for over 6 weeks (8). Purine base incorporation is qualitatively identical to that found for T. cruzi both trypanosomes lack the adenine deaminase which is found in Leishmania (Fig. 6.7). Purine ribonucleosides were utilized slightly more efficiently than their corresponding purine bases. 

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