2 -Deoxyuridine, structure

S. Sim, and R. H. Raper. 5-Substituted deoxyuridines - structural requirements for antiviral activity... 

Methotrexate (MTX, chemical structure shown in Fig. 1.) competitively inhibits the dehyrofolate reductase, an enzyme that plays an essential role in purine synthesis. The dehydrofolate reductase regenerates reduced folates when thymidine monophosphate is formed from deoxyuridine monophosphate. Without reduced folates cells are unable to synthesize thymine. Administration of N-5 tetrahydrofolate or N-5 formyl-tetrahydrofolate (folinic acid) can bypass this block and rescue cells from methotrexate activity by serving as antidote. 

Stein and co-workers have reported the structure of an unusual tetranuclear platinum(II) complex possessing both ammine and carbonato ligands.325 During a study of the reaction of cisplatin with Ag+, followed by the addition of 2 -deoxyuridine to afford platinum blue -like products from aqueous solution (pH < 2), a colorless minor product was isolated from the reaction mixture. X-ray crystallography confirmed that the product was a cyclo tetra-cation... 

P—S bond is elongated to 196.5 pm and the P—0(H) bond shortened to 148 pm.164 The structures of the m-vinyl carbonate (136)165 and the cyclic phosphonic anhydride (96)123 have been determined, and for the latter compound the ring was found to be almost planar. A -Ray diffraction data of deoxyuridine phosphate,166 phospholipid multilayers,167 nucleotides,168 and skeletal muscle169 have been analysed. The crystal structure of the phosphazene (137) has been established.170... 

Fig. 2. Structure of fluorouracil (5-FU) and floxuridine (5-fluoro-2 -deoxyuridine, FdUrd).

During thymine formation the coenzyme is oxidized to dihydrofolate, which must be reduced by dihydrofolate reductase to complete the catalytic cycle. A possible mechanistic sequence for thymidylate synthase, an enzyme of known three-dimensional structure,354/418-4213 is given in Fig. 15-21. In the first step (a) a thiolate anion, from the side chain of Cys 198 of the 316-residue Lactobacillus enzyme, adds to the 5 position of the substrate 2 -deoxyuridine monophosphate... 

Chatgilialoglu C, Gimisis T, Guerra M, Ferreri C, Emanuel CJ, Horner JH, Newcomb M, Pedulli GF (1998) Spectra and structure of the 2 -deoxyuridin-1 -yl radical. Tetrahedron Lett 39 3947-3950... 

A metabolic pathway that has received considerable attention is the conversion of 2 -deoxyuridine 5 -monophosphate (dUMP, 6.60) to thymidine 5 -monophosphate (TMP, 6.61) (Scheme 6.13). Without an adequate supply of TMP, a cell or bacterium cannot create DNA for cell division. Therefore, blocking TMP synthesis is an attractive method for slowing the advancement of certain cancers and bacterial infections. Important molecules in the methylation of dUMP are the various folic acid derivatives folic acid (FA, 6.62), dihydrofolic acid (DHF, 6.63), tetrahydrofolic acid (THF, 6.64), and N5, A1 "-methylene tetrahydrofolic acid (MTHF, 6.65) (Figure 6.23). These structures... 

Application of this reaction to 2, 2-anhydrouridine (LXXXVII) led to a 3-substituted nucleoside (CIV) which, upon acylation followed by reduction with Raney nickel, yielded 3-deoxyuridine (CV, R = uracilyl). Reductive cleavage of CV, by the sodium-liquid ammonia procedure,72 afforded 3-deoxy-D-en/fAro-pentose ( 3-deoxy-D-ribose ), a result which establishes position 3 as the site originally containing the ethylthio function. The authors suggest,248 as a plausible route to CIV, the initial formation of the anion CII, followed by formation of the 2,3-anhydride structure. The anhydride (CIII) is then attacked, at C3, by the ethanethiol ion, to yield... 

Figure 4 Molecular structures of five DNA nucleosides 2 -deoxyuridine (dU), 2 -de-oxythymidine (dT), 2 -deoxycytidine (dC), 2 -deoxyguanosine (dG), and 2 -deoxyadeno-sine (dA).

The structures of these materials are as yet unknown. Interestingly, a tetranuclear complex containing four cw-(NH3)2Ptn units and two /t4-car-bonato ligands, [Pt4(NH3)8(C03)2](N03)4, has been isolated from a preparation of a Pt deoxyuridine blue and characterized by X-ray crystal structure analysis [85]. The four Pt ions in this complex form roughly a square of sides of ca. 3.18-3.28 Aand consequently do not form metal-metal bonds. 

Figure 3-8. Structural drawings of IV-acetyl-l-aminopyrene (PAAc), 5-(A-carboxyl-l-aminopyrenyl)-2 -deoxyuridine (PAdU) and lV-(l-pyrenyl)-l-methyluracyl-5-carboxamide (PAUMe)...

The crystal structure of 6-methyl-2 -deoxyuridine [MEDOUR] has a very simple finite chain (Fig. 17.16). Because the nucleoside is in the syn form as 6-methyl-... 

The crystal structure of 5-chloro-2-deoxyuridine [CLDOUR] has a very simple pattern with two infinite chains (Fig. 17.21). One is through the O -H groups, and the other through the minor component of a three-center bond formed by 0(30-H. It strongly resembles a carbohydrate hydrogen-bonding pattern. A very simple scheme is also formed by 2-chloro-2 -deoxyuridine [CDURID] with a short finite chain and a separate link from the primary alcohol (Fig. 17.22). 

The Rayner group has reported several examples of the use of dynamic nucleic acid decoration for stabilizing structures of interest. In the first of these, described in 2004 [45], a mixture consisting of a self-complementary DNA hexamer bearing a 2 -amino-2 -deoxyuridine at the 3 -terminus with a pool of three aldehydes (51-53, Fig. 19) and sodium cyanohydride was generated. Analysis of aliquots of the... 

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