2 -Deoxyribose, structure

Once a pool of deoxyribonucleotides has formed, the individual deoxyribonucleotides cannot function effectively as enzyme cofactors but can only be utilized for DNA formation. The deoxyribose structure seems to preclude enzyme cofactor function. [In the evolution of macromolecules, it is conceivable that RNA served as a template for DNA formation in the presence of a reverse transcriptase (Verma, 1977).] Interestingly, it has been found that RNA serves as a primer for DNA replication (Kornberg, 1976). 

Watson J D and Crick F H C 1953 A structure for deoxyribose nucleic acid Nature 171 737-8... 

Watson and Crick published their work in a pa per entitled A Structure for Deoxyribose Nucleic Acid in the British journal A/ature on April 25 1953 In addition to being one of the most important pa pers of the twentieth century it is also remembered for one brief sentence appearing near the end... 

Cytosine was isolated from hydrolysis of calf thymus in 1894 and by 1903 its structure was known and it had been synthesized from 2-ethylthiopyrimidin-4(3H)-one. The acid hydrolysis of ribonucleic acid gives nucleotides, among which are two cytidylic acids, 2 -and 3 -phosphates of cytidine further hydrolysis gives cytidine itself, i.e. the 1-/3-D-ribofuranoside of cytosine, and thence cytosine. The deoxyribonucleic acids likewise yield deoxyribonucleotides, including cytosine deoxyribose-5 -phosphate, from which the phosphate may be removed to give cytosine deoxyriboside and thence cytosine. 

Watson, J.D., Crick, F.H.C. Molecular structure of nucleic acids. A structure for deoxyribose nucleic acid. Nature 171 737-738, 1953. 

Figure 12.16), can insert between the stacked base pairs of DNA. The bases are forced apart to accommodate these so-called intercalating agents, causing an unwinding of the helix to a more ladderlike structure. The deoxyribose-phosphate backbone is almost fully extended as successive base pairs are displaced 0.7 nm from one another, and the rotational angle about the helix axis between adjacent base pairs is reduced from 36° to 10°. 

As noted previously, RNA is structurally similar to DNA but contains ribose rather than deoxyribose and uracil rather than thymine. There are three major kinds of RNA, each of which serves a specific function. All three are much smaller molecules than DNA, and all remain single-stranded rather than double-stranded. 

Attached by a covalent bond to carbon atom 1 of the deoxyribose ring is an amine (and therefore a base), which may be adenine, A (22) guanine, G (23) cytosine, C (24) or thymine, T (25). In RNA, uracil, U (26), replaces thymine. The base bonds to carbon atom 1 of deoxyribose through the nitrogen of the —NH— group (printed in red) and the compound so formed is called a nucleoside. All nucleosides have a similar structure, which we can summarize as the shape shown in (27) the lens-shaped object represents the attached amine. 

The cholesterol-lowering drug atorvastatin, marketed as Lipitor, is an example where biocatalysis research has been applied extensively and is in industrial use. The enzyme 2-deoxyribose-5-phosphate aldolase (DERA) has been a target of directed evolution for the production of atorvastatin intermediates [8,9,71]. DeSantis and coworkers [8,9] used structure-based... 

DeSantis, G., Liu, J., Clark, D.R et al. (2003) Structure-based mutagenesis approaches toward expanding the substrate specificity of D-2-deoxyribose-5-phosphate aldolase. Bioorganic and Medicinal Chemistry, 11, 43-52. 

Figure 3. Structure of major DNA adduct detected in many in vivo systems as a result of metabolic activation of benzo[a]pyrene or the reaction of anti-B[alPDE with DNA jji vitro dR=deoxyribose moiety.

A more complex structure is that of leinamycin 45 (Scheme 15), a material with potent cytotoxic and antitumor properties, isolated from a Streptomyces sp. A 1,2 dithiolane-3-one ring is spiro fused to a complex macrolactam96 (and references therein). Leinamycin has the remarkable ability to cleave DNA. In brief, leinamycin reacts with a thiol and, after a profound rearrangement, forms an episulfonium ion. This ion alkylates the N7 position of guanosine residues in double stranded DNA an unstable adduct is depurinated by hydrolysis of the glycosidic bond between the alkylated base and a deoxyribose residue. Some structurally less complex l,2-dithiolane-3-one 1-oxides have a similar DNA cleaving ability.97... 

Figure 3.3 Chemical structure of (a) ribose and (b) 2 -deoxyribose, the nucleotide pentoses found in RNA and DNA respectively. The differences in chemical structure are highlighted by the dotted circles...

Figure 4.13 The structure of part of a molecule of DNA. The deoxyribose residues are linked by phosphodiester bonds between the 3 OH of one nucleoside and the 5 OH of the next.

In nature, eight common nucleotides exist, four found in DNA and four in RNA. In the standard abbreviations for DNA nucleotides, a lowercase d specifies the presence of deoxyribose. RNA nucleotides lack this designation. Nucleosides have names of one word (e.g., deoxyadenosine, cytidine, and uridine). The ending monophosphate completes the nucleotide names. Table 16.1 lists correct names for all common nucleotides and nucleosides, and Figure 16.9 shows linkages and structures for all eight nucleotides. 

The main structure of a nucleotide is based on a simple saccharide, or sugar. The sugar that is used to make DNA is 2-deoxyribose. The sugar that is used to make RNA is ribose. 

In 1953, James Watson and Francis Crick (Figure 9) suggested a structure for deoxyribose nucleic acid (DNA). The suggestion had important novel features. One was that it had two helical chains, each coiling around the same axis but having opposite direction. The two helices going in opposite direction, and thus complementing each other, is a simple consequence of the twofold symmetry of the whole double... 

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