Cytidine, chemical structure

It was snbseqnently discovered that the first enzyme in the pathway for isoleucine synthesis, which is threonine deaminase, was inhibited by isoleucine in an extract of E. coli. No other amino acid caused inhibition of the enzyme. Threonine deaminase is, in fact, the rate-limiting enzyme in the pathway for isoleucine synthesis, so that this was interpreted as a feedback control mechanism (Fignre 3.13(a)). Similarly it was shown that the hrst enzyme in the pathway for cytidine triphosphate synthesis, which is aspartate transcarbamoylase, was inhibited by cytidine triphosphate (Fignre 3.13(b)). Since the chemical structures of isoleucine and threonine, or cytidine triphosphate and aspartate, are completely different, the qnestion arose, how does isolencine or cytidine triphosphate inhibit its respective enzyme The answer was provided in 1963, by Monod, Changenx Jacob. 

The aminoaqfl-4-aminohexosyl-cytosine group of antibiotics is classified based on chemical structures (Fig. 4.11) each of which contains a cytosine base. Included in this group are blasticidin S, gougerotin, amicetin and bamicetin [46]. These antibiotics are not used therapeutically. However blasticidin S is an important antifungal used on rice crops. Only the crystal structure of blasticidin S bound to the ribosome is available. The chemical structure of blasticidin S resembles that of pep-tidyl-cytidine, although not as closely as puromycin resembles a tyrosylated adenosine (Fig. 4.11). 

It should therefore be possible to design chemical structures, modeled after known or putative reaction intermediates that resemble postulated transition states. They may exhibit high affinities for the reactive sites of enzymes and therefore function as effective, but reversible, inhibitors. A successful example is the potent and specific cytidine deaminase inhibitor 3,4,5,6-tetrahydrouridine, which effectively blocks the conversion of cytidine to uridine. It was similarly demonstrated that 1,6-dihydro-6-hydroxymethylpurine effectively blocked the deamination of adenine to hypoxanthine by adenine deaminase (Eq. 2.13). 

Fig. 24.30 (a) Synthetic steps towards a paira-ter/-butyl-calix[4]arene-bonded silica stationary phase [94]. (b) Chemical structure of para-tert-butyl-calix[8]arene-bonded silica gel stationary phase [95]. (c) Isocratic separation of nucleosides cytidine, uridine, guanosine and adenosine on an Aren Si 60 column with 0.02 M NaH2P04 (pH 3.5) as mobile phase (x-axis time in min y-axis absorbance at 254 nm) [93]. (Reprinted from Ref [93])... 

Figure 10 Chemical structures of adenosine 5 -monophosphate (n = 1 AMP ), adenosine 5 -diphosphate (n = 2 ADP "), and adenosine 5 -triphosphate (n = 3 ATP ) as well as of cytidine 5 -monophosphate (n = 1 CMP, cytidine 5 -diphosphate (n = 2 CDP ), and cytidine 5 -triphosphate (n = 3 CTP ) in their dominating anti conformation [11-14,50]. Note, the triphosphate chain in nucleoside 5 -triphosphates (NTP ) is labeled a, P, and y, where y refers to the terminal phosphate group (see also Figure 9) for nucleoside 5 -diphosphates (NDP ) the situation is analogous with a and P (see Figure 9). The adenine and cytosine residues in the nucleotide structures shown above may be replaced by one of the other nucleobase residues shown in Figiue 1 if this substitution is done in the way the bases are depicted within the plane (Figure 1), then the anti conformation will also result for the corresponding nucleoside 5 -phosphates. The abbreviations AMP, ADP , ATP , IMP, etc. in this text always represent the 5 -derivatives 2 - and 3 -derivatives are defined by 2 AMP, 3 AMP, etc. in a few instances where uncertainties might otherwise occur, the abbreviations 5 AMP , 5 ADP , etc. are also used.

Carbon-13 magnetic resonance spectra of the naturally occurring cytidines have been described in several papers.79-82 The electronic structure of the compounds is reflected in the carbon-13 shifts. For instance, the observed chemical shifts for these and other pyrimidine and purine nucleosides were correlated, at least qualitatively, with the calculated charge densities (see Section VIII) and with the known reactivity of these molecules. It is difficult to draw conclusions from the carbon-13 spectra about the tautomerism of cytosine. 

The first scientific articles from the IKhPS were submitted for publication in the early 1960s, among them being Nikolay s reports on his work in the new field. His major project in nucleotide chemistry was specific chemical modifications of heterocyclic bases. Reactions of hydroxylamine with cytidine and uridine were studied in detail and a new reagent, O-methylhydroxylamine, was proposed for modification of cytidine. These investigations aimed at the development of efficient methods for sequencing and analysis of the secondary structure of polynucleotides. Later, a reaction of chloroacetaldehyde with adenosine and cytidine was discovered and used for preparation of fluorescent polynucleotide derivatives. 

Therapeutic Function Antineoplastic, Antiviral Chemical Name Cytidine, 2 -deoxy-2, 2 -difluoro Common Name Difluorodeoxycytidine Gemcitabine Structural Formula ... 

High-frequency, p.m.r. spectroscopy has proved to be an extremely important tool in studies of the structures, conformations, and inter-and intra-molecular base-stacking interactions of nucleosides and nucleotides. The temperature dependence of the chemical shift of the base proton at position 6 (H-6) has been studied at 220 MHz for uridine (36), cytidine (38), and a number of their mono- (37, 39) and... 

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