Thymidine structure

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. 

The 2 -chloro and 2 -bromo congeners of either 748 (FIAC) or 758 (FMAU) are more cytotoxic than FIAC and FMAU, suggesting that these chloro and bromo nucleosides, in contrast to the 2 -fluoro compounds, are comparatively better substrates for deoxycytidine kinase of human lymphocytes than the substrates for viral-specific thymidine kinase. The disposition of the 2 -fluoro group may also be important from the biological viewpoint. It should be noted that the structural difference between RNA and DNA is at the 2 -position. The ribo type of analog (738) of FIAC is 10 times less effective in suppression of HSV replication than is FIAC. Thus Fox, and Watanabe and coworkers concluded that the 2 - up fluorine disposition and the species of the substituent at C-5 are the two important factors influencing antiviral activity. Nevertheless, the mechanism of action of 2 -deoxy-2 -fluorocytidine (737) on certain herpes viruses, including HSV-1... 

The crystal and molecular structure of the 44, 45, and C5-vinylferro-cenyl-thymidine show that the substituted cyclopentadienyl ring is essentially co-planar with the nucleobase (164). DFT calculations indicate that, irrespective of the extent of saturation in the bridging C2-unit in ethynyl-, vinyl- or ethyl-ferrocenyl-C5-thymidine, a similar amount of spin density is transferred to the nucleobase (Fig. 48). The reduction potentials for these compounds are shifted little compared to the parent ferrocenyl derivatives. 

Incorporation of a flavin electron donor and a thymine dimer acceptor into DNA double strands was achieved as depicted in Scheme 5 using a complex phosphoramidite/H-phosphonate/phosphoramidite DNA synthesis protocol. For the preparation of a flavin-base, which fits well into a DNA double strand structure, riboflavin was reacted with benzaldehyde-dimethylacetale to rigidify the ribityl-chain as a part of a 1,3-dioxane substructure [49]. The benzacetal-protected flavin was finally converted into the 5 -dimethoxytri-tyl-protected-3 -H-phosphonate ready for the incorporation into DNA using machine assisted DNA synthesis (Scheme 5a). For the cyclobutane pyrimidine dimer acceptor, a formacetal-linked thymine dimer phosphoramidite was prepared, which was found to be accessible in large quantities [50]. Both the flavin base and the formacetal-linked thymidine dimer, were finally incorporated into DNA strands like 7-12 (Scheme 5c). As depicted in... 

MP3 optimized conformations of the pyrimido[l,6-c][l,3]oxazine 285 ( = 1) were calculated to see structural similarities with thymidine <1996NN1481>. 

Ribonucleic acid (RNA) Molecules including messenger RNA, transfer RNA, ribosomal RNA, or small RNA. RNA serves as a template for protein synthesis and other biochemical processes of the cell. The structure of RNA is similar to that of DNA except for the base thymidine being replaced by uracil. 

An interesting idea was to use a monolith column to perform dual functions of online SPE and chromatographic separation. Because of the porous structure of a monolith column and its very low backpressure, plasma or diluted plasma can be directly injected. Plumb et al. (2001) used this approach to quantitate an isoquinoline drug and 3 -azido-3 -deoxy thymidine (AZT). Diluted plasma samples (plasma water 1 1) were injected directly into a Chromolith Speed ROD RP-18e column... 

Tipson devoted most of his years in Levene s laboratory accomplishing seminal work on the components of nucleic acids. To determine the ring forms of the ribose component of the ribonucleosides he applied Haworth s methylation technique and established the furanoid structure for the sugar in adenosine, guanosine, uridine, and thymidine. He showed that formation of a monotrityl ether is not a reliable proof for the presence of a primary alcohol group in a nucleoside, whereas a tosyl ester that is readily displaced by iodide affords clear evidence that the ester is at the 5-position of the pentofuranose. Acetonation of ribonucleosides was shown to give the 2, 3 -C -isopropyl-idene derivatives, which were to become extensively used in nucleoside and nucleotide chemistry, and were utilized by Tipson in the first chemical preparation of a ribonucleotide, inosinic acid. 

Taylor, J.S., Garrett, D.S., Cohrs, M.P. Solution-state structure of the Dewar pyrimidinone photoproduct of thymidylyl-(3 -5 )-thymidine. Biochemistry 1988, 27, 7206-7215. 

Aciclovir is a member of a group of nucleoside derivatives termed acyclonucleosides, in that there is an incomplete sugar ring. The structural relationship to 2 -deoxyguanosine should be very clear. Aciclovir is converted into its monophosphate by the viral enzyme thymidine kinase - some viruses also possess enzymes that facilitate their replication in the host cell. The viral enzyme turns out to be much more effective than that of the host cell, and conversion is, therefore, mainly in infected cells. The monophosphate is subsequently converted into the triphosphate hy the host cell enzymes. Aciclovir triphosphate inhibits viral DNA polymerase, much more so than it does the host enzyme, and so terminates DNA replication. 

The base sequence and the tertiary structure of the yeast tRNA specific for phenylalanine (tRNA " ) is typical of all tRNAs. The molecule (see also p.86) contains a high proportion of unusual and modified components (shaded in dark green in Fig. 1). These include pseudouridine (T), dihydrouridine (D), thymidine (T), which otherwise only occurs in DNA, and many methylated nucleotides such as 7-methylguanidine (m G) and—in the anticodon—2 -0-methylguanidine (m G). Numerous base pairs, sometimes deviating from the usual pattern, stabilize the molecule s conformation (2). 

Fig. 18. Thymidine (dT) and an oxepanyl analogue (oT). Structures on the bottom (taken from ref. 149) show minimized conformers for both dT and oT, emphasizing the similarity in the disposition of the base and the C-4/C-6 hydroxymethyl group.

Cotton, F. A., Hazen, E. E., Jr., and Legg, M. J. (1979). Staphylococcal nuclease Proposed mechanism of action based on structure of enzyme-thymidine 3, 5 -bisphosphate-calcium ion complex at 1.5-A resolution. Proc. Natl. Acad. Sci. U.S.A. 76, 2551-2555. 

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