Nucleosides, chemical structure

Ethynylcytidine [l-(3-C-ethynyl-p-D-ribopentafuranosyl)-cytosine] (ETC) is a novel nucleoside that was foimd to be highly cytotoxic (53-55). By combination of ETC with NOAC, we synthesized the new lipophilic derivative NOAC-ETC [3 -C-ethynylcytidylyl-(5 —>5 )-N" -octadecyl-l-p-D-arabinofura-nosylcytosine]. The chemical structure of ETC-NOAC is shown in Fig. 1. 

FIGURE 9. The chemical structure of nucleoside triphosphates (NTP and dNTP)... 

Gemcitabine [gem SITE ah bean] is an analog of the nucleoside deoxycytidine its chemical structure is 2 2 -difluorodeoxycytidine (dFdC). Its use is indicated in the first-line treatment of locally advanced or metastatic adenocarcinoma of the pancreas. It has also shown some activity against other tumors. 

Fig. 17.1. Chemical structures of and atomic numbering scheme in the nucleosides, shown for uridine, deoxyadenosine, and the antibiotic arabinocytidine...

Fig. 4.11 Chemical structures of antibiotics. Chemical structures of nucleosides are provided in the top row for comparison with the antibiotics shown in the second row. The third row shows chemical structures of antibiotics that only weakly resemble the nucleosides to which they have been compared.

The prototypical aminoacylated nucleoside analogue antibiotic is puromycin which inhibits the protein translation in all three domains of life. The chemical structure of puromycin is the same as that of tyrosylated adenosine, except for the presence of three added methyl groups and the replacement of an ester bond with an amide bond (Fig. 4.11). Puromycin mimics tyrosyl-tRNA so well that it binds to the A-site and gets incorporated into an elongating peptide. This leads to termination of translation because puromycin terminated peptides fall off the ribosome. Puromycin derivatives have been used crystallographically as peptidyl transferase substrates and have contributed to our understanding of the structure of the peptidyl transferase site (Fig. 4.5) [11, 16, 45],... 

The three part so-called cocktail used to treat HIV positive patients typically comprise a proteinase inhibitor, such as those discussed in Chapter 1 a nucleoside-based reverse transcriptase inhibitor, such as those in Chapter 6, and a non-nucleoside inhibitor of reverse transcriptase (NNRTI). Most of the compounds in the first two classes share a good many structural features with other agents in the class. Chemical structures of the various NNRTIs on the other hand have little in common. Capravirine (103), is notable in the fact that it fails to include any of the fused ring systems that provide the nucleus for other compounds in this class. Chlorination of 3-methylbutyraldehyde (94) provides one of the components for building the imidazole ring. For bookkeeping purposes, the condensation of 94 with 0-benzyl glyoxal and ammonia can be... 

Nucleoside analogue reverse transcriptase inliibitors are diTigs of diverse chemical structure that act by non-competitive inliibition of HIV-l reverse transcriptase. 

Dideoxycytidine (DDC, zalcitabine), a nucleoside analogue that also inhibits reverse transcriptase, is more active than zidovudine in vitro, and (unlike zidovudine) does not suppress erythro-poiesis. DDC is not without toxicity, however, and a severe peripheral neurotoxicity, which is dose-related, has been reported. The chemical structures of DDC and of another analogue with similar properties, 2 3 -dideoxyinosine (DDI, didanosine), are presented in Fig. 10.25 (G, H, respectively). 

Fig. 6.4. Chemical structure of the purines and pyrimidine bases as well as representative nucleosides and nucleotides.

Phosphodiester bonds are what make up the backbone of DNA and RNA molecules. These bonds provide the linkage that holds together the individual nucleotides or nucleosides in DNA and RNA. Enzymes called polymerases catalyze their formation (DNA polymerases for DNA and RNA polymerases for RNA). Take a look at the picture below to see the chemical structure of a phosphodiester bond. 

FIGURE 3.46 Bottom chemical structure of a polynucleotides (DNA, RNA). Top chemical structure of nucleoside bases. 

The chemical structure of the polynucleotide being produced in de novo copolymerizations depends on the kind of nucleoside triphosphates used as well as on the experimental conditions. In the joint polycondensation of a mixture of d-GTP and d-CTP, the two homopolymers, poly(dG) and poly(dC), as well as the dpuble-strand poly(dG) poly(dC) consisting of one of each kind of homopolymer joined together, are produced. The complexity one is ascribed to such complexes from two homopolymers. 

In the area of biologically active natural products, m.s. has been used to identify the position of acylation of partially acetylated kanamycins (see Chapter 18 for further reference to relevant antibiotic work) and in an examination of pyrimidine 5, 6-anhydronucleosides. The Field Desorption spectra of 13 nucleoside antibiotics all exhibited intense molecular ions [and (M + 1)+ ions] and fragment ions characteristic of their chemical structures. ... 

Table 1 (section 3.2.1.4) contains a list of the nucleosides which have been polymerized into polynucleotides, their abbreviations used and examples of their chemical structure. In general the lUPAC-IUB nomenclature [79il] has been followed. 

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