Ribose ring form

C13-0065. The five-carbon sugar ribose can form a six-membered ring, ribop Tanose, that differs from... 

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. 

Nucleic acids have two kinds of pentoses. The recurring deoxyribonucleotide units of DNA contain 2 -deoxy-D-ribose, and the ribonucleotide units of RNA contain D-ribose. In nucleotides, both types of pentoses are in their j3-furanose (closed five-membered ring) form. As Figure 8-3 shows, the pentose ring is not planar but occurs in one of a variety of conformations generally described as puckered. ... 

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. 

A major objection to the RNA world is the lack of stability of ribose and the inability to demonstrate the nonenzymatic synthesis of ribose in significant amounts. Even if ribose were present, it would be largely in the pyranose ring forms. Initial formation of the 5-phosphate would be required to allow formation of a nucleotide with a furanose ring. 

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. 

Most 5- and 6-membered sugars are found in nature as pyranose ring forms. Why is ribose in RNA in the furanose ring form ... 

Answer Without the base, the ribose ring can be opened to generate the noncyclic aldehyde form. This, and the loss of base-stacking interactions, could contribute significant flexibility to... 

This Sjsi2 reaction has to happen with inversion, proving that the base and the 3 -OH group are on opposite sides of the ribose ring. The cyclized product is useful too. If it is reacted with azide ion the ring reopens with inversion in another Sn2 reaction and AZT is formed. 

The bases are in syn or anti orientation. The orientation of the base relative to the sugar moiety is defined by torsion angle x which is constrained by steric interactions, and by the anomeric effect. The main conformations are referred to as syn and anti (see Fig. 17.5). In syn, j X is close to 0° (sp for torsion angle definition, see Box 13.3 Fig. 13.12), and the base is I oriented "above the ribose ring causing steric interactions which in the anti conformation with x close to 180° (ap) are avoided. The anti conformation is therefore preferred and is the j only form observed in double-helical DNA and RNA. An exception is the left-handed Z-DNA with alternating purine/pyrimidine nucleotide sequence where the purines are in the syn conformation. 

In the crystal structure of 5-chlorouridine [CLURID01], the inter- and intramolecular ( ) 0(2 )-H- -0(3 )-H -0(2 )-H bonds form an infinite chain (Fig. 17.20). The primary alcohol 0(5 )-H forms only a weak two-center bond to a ribose ring oxygen which is not part of the major pattern. 

The same nomenclature applies to the furanose ring form of fructose, except that a and p refer to the hydroxyl groups attached to C-2, the anomeric carbon atom (see Figure 11.5). Fructose forms both pyranose and furanose rings. The pyranose form predominates in fructose free in solution, and the furanose form predominates in many fructose derivatives (Figure 11.6). Pentoses such as d-ribose and 2-deoxy-d-ribose form furanose rings, as we have seen in the structure of these units in RNA and DNA. 

In de novo synthesis of pyrimidines, the ring is synthesized first and then it is attached to ribose to form a pyrimidine nucleotide (Figure 25.2). Pyrimidine rings are assembled from bicarbonate, aspartic acid, and ammonia. Although ammonia can be used directly, it is usually produced from the hydrolysis of the side chain of glutamine. 

Orotate Acquires a Ribose Ring from PRPP to Form a Pyrimidine Nucleotide and Is Converted into Uridylate... 

Synthesis of Thymidine nucleotides first requires deoxyribonucleotide synthesis. The enzyme responsible for this step is Ribonucleotide Reductase. This enzyme acts on oxynucleotides in their diphosphate form. Thioredoxin, a small protein, is oxidized as the 2 hydroxyl group on the ribose ring is reduced. Oxidized Thioredoxin (S-S) is then reduced by FADH2 and NADPH. The products are the respective deoxynucleotide diphosphates which are further phosphorylated and then used for DNA synthesis. 

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