Ribose rings

FIGURE 1.9 (a) Amino acids build proteins by connecting the n-carboxyl C atom of one amino acid to the n-amino N atom of the next amino acid in line, (b) Polysaccharides are built by combining the C-1 of one sugar to the C-4 O of the next sugar in the polymer, (c) Nucleic acids are polymers of nucleotides linked by bonds between the 3 -OH of the ribose ring of one nucleotide to the 5 -P04 of its neighboring nucleotide. All three of these polymerization processes involve bond formations accompanied by the elimination of water (dehydration synthesis reactions). 

The association between RNase A and 3 -UMP or 3 -dUMP has been studied by P n.m.r. and kinetic methods, respectively. In both cases the participation of two dissociable groups at the active site of the enzyme was demonstrated, in agreement with n.m.r. and A -ray - studies on the binding of 3 -CMP to RNase. In the binding of Tj RNase to purine nucleotide monophosphates, the phosphate group appears to have an important effect while the ribose ring is relatively unimportant. ... 

The dependence of cross-correlated relaxation on the projection angle between the two dipole vectors can be exploited to determine local conformations in ribose rings. 

Nucleotides and nucleosides have emerged as important molecules in medicinal chemistry. In the 1950s, Elion and Hitchings discovered that 6-mercaptopurine had antitumor properties. This pioneering discovery opened the door for many subsequent studies of nucleotide derivatives as therapeutics. Acyclovir (8.3), a nucleoside that lacks two carbon atoms of its ribose ring, is effective in the treatment of herpes infections. Allopurinol, a purine derivative, is useful in the treatment of gout. 

Nucleic acids are polymeric nucleotides in which phosphate esters link ribose or deoxyribose molecules through the C OH of one and the C OH of the other. In rna, the aglycone nitrogen bases are cytosine, adenine, guanine, and uracil. In dna, thymine replaces uracil. The rna polymer is like that of dna, except that a CH, replaces the OH group on C of the ribose ring. 

The B form of fibrous DNA is stable under conditions of high ( 93%) humidity but at 75% humidity it is converted into A-DNA in which the base pairs are inclined to the helix axis by about 13° and in which the ribose rings are primarily C3 -endo rather than C2 -endo. 

Reaction occurs at other nitrogen atoms as well as the oxygen atom of the base and of the ribose ring to a lesser extent. Adenine is alkylated preferentially at N-l and cytosine and thymine at the corresponding position (N-3) almost exclusively. Uridine and thymidine react very slowly. Adenine is also alkylated at N-3, N-7 and at the exocyclic N-6. 

Most ribozymes, as well as RNase P,805,806 require one or two metal ions for activity.807 Magnesium ions predominate and many Mg24 ions are bound at distinct sites in crystalline ribozymes. Hammerhead and hairpin ribozymes work reasonably well with monovalent ions. One proposed mechanism is for an HO ion bound to the Mg2+ to remove H+ from the 2 - OH of the ribose ring as follows ... 

A relative of the kinases is adenylate cyclase, whose role in forming the allosteric effector 3, 5 -cyclic AMP (cAMP) was considered in Chapter 11. This enzyme catalyzes a displacement on Pa of ATP by the 3 -hydroxyl group of its ribose ring (see Eq. 11-8, step a). The structure of the active site is known.905 Studies with ATPaS suggest an in-line mechanism resembling that of ribonuclease (step a, Eq. 12-25). However, it is Mg2+ dependent, does not utilize the two-histidine mechanism of ribonuclease A, and involves an aspartate carboxylate as catalytic base.906 All isoforms of adenylate cyclase are activated by the a subunits of some G proteins (Chapter 11). The structures907 of Gsa and of its complex with adenylate kinase905 have been determined. The Gsa activator appears to serve as an allosteric effector. 

Bound NAD+ is also present in S-adenosylhomo-cysteine hydrolase,119 120 which catalyzes the irreversible reaction of Eq. 15-14. Transient oxidation at the 3 position of the ribose ring facilitates the reaction. The reader can doubtless deduce the function that has been established for the bound NAD+ in this enzyme. However, the role of NAD in the urocanase reaction (Eq. 15-15) is puzzling. This reaction, which is the second step in the catabolism of histidine, following Eq. 14-44, appears simple. However, there is no obvious... 

Hydrolysis of deoxyadenosylcobalamin by acid (1 M HC1,100°, 90 min) yields hydroxycobalamin, adenine, and an unsaturated sugar (Eq. 16-33). The initial reaction step is thought to be protonation of the oxygen of the ribose ring. 

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