5-Ribonucleotides

The discovery of nbozymes (Section 28 11) in the late 1970s and early 1980s by Sidney Altman of Yale University and Thomas Cech of the University of Colorado placed the RNA World idea on a more solid footing Altman and Cech independently discovered that RNA can catalyze the formation and cleavage of phosphodiester bonds—exactly the kinds of bonds that unite individual ribonucleotides in RNA That plus the recent discovery that ribosomal RNA cat alyzes the addition of ammo acids to the growing peptide chain in protein biosynthesis takes care of the most serious deficiencies in the RNA World model by providing precedents for the catalysis of biologi cal processes by RNA... 

THACRYLIC ACID AND DERIVATIVES] (Vol 16) b-Thioglycinamide ribonucleotide dideazafolate [119637-95-5]... 

Flavor Enhancers. Flavor enhancers have the abihty to enhance flavors at a level below which they contribute any flavor of their own. Worldwide, the most popular flavor enhancers are monosodium L-glutamate [142-47-2] (MSG), NaC HgNO, and the 5 -ribonucleotides disodium 5 -inosinate [131-99-7] (IMP), and disodium S -guanjIate [85-75-5] (GMP), C QH 2-N50gP -2Na. 

The intensity of "umami" increases linearly with a logarithmic increase in the concentration of MSG. The synergistic effect of MSG with 5 -ribonucleotides is expressed by the following relation... 

Clindamycin 3-phosphate [28708-34-17, antibacterially inactive in vitro, and the ribonucleotides clindamycin 3-(5 -cytidylate) [31186-90-0], clindamycin 3-(5 -adenylate) [31186-91-1], clindamycin 3-(5 -uridylate) [36010-69-2], and clindamycin 3-(5 -guanylate) [36010-70-5], all inactive in vitro, can be generated... 

The benzoylformate ester can be prepared from the 3 -hydroxy group in a deoxy-ribonucleotide by reaction with benzoyl chloroformate (anh. Pyr, 20°, 12 h, 86% yield) it is cleaved by aqueous pyridine (20°, 12 h, 31% yield), conditions that do not cleave an acetate ester. ... 

The most conspicuous use of iron in biological systems is in our blood, where the erythrocytes are filled with the oxygen-binding protein hemoglobin. The red color of blood is due to the iron atom bound to the heme group in hemoglobin. Similar heme-bound iron atoms are present in a number of proteins involved in electron-transfer reactions, notably cytochromes. A chemically more sophisticated use of iron is found in an enzyme, ribo nucleotide reductase, that catalyzes the conversion of ribonucleotides to deoxyribonucleotides, an important step in the synthesis of the building blocks of DNA. 

Figure 1.9 Examples of functionally important intrinsic metal atoms in proteins, (a) The di-iron center of the enzyme ribonucleotide reductase. Two iron atoms form a redox center that produces a free radical in a nearby tyrosine side chain. The iron atoms are bridged by a glutamic acid residue and a negatively charged oxygen atom called a p-oxo bridge. The coordination of the iron atoms is completed by histidine, aspartic acid, and glutamic acid side chains as well as water molecules, (b) The catalytically active zinc atom in the enzyme alcohol dehydrogenase. The zinc atom is coordinated to the protein by one histidine and two cysteine side chains. During catalysis zinc binds an alcohol molecule in a suitable position for hydride transfer to the coenzyme moiety, a nicotinamide, [(a) Adapted from P. Nordlund et al., Nature 345 593-598, 1990.)...

Nordlund, P., Sjoberg, B.-M., Eklund, H. Three-dimensional stmcture of the free radical protein of ribonucleotide reductase. Nature 345 593-598, 1990. 

Uhlin, U., Eklund, H. Structure of ribonucleotide reductase protein Rl. Nature 370 553-559, 1994. 

FIGURE 11.13 Structures of the four cotntnou ribonucleotides—AMP, GMP, CMP, and UMP—together with their two sets of full uatnes, for example, adeuosiue 5 -mouophosphate and adenylic acid. Also shown is the nucleoside 3 -AMP. 

Nucleic acids are linear polymers of nucleotides linked 3 to 5 by phosphodi-ester bridges (Figure 11.17). They are formed as 5 -nucleoside monophosphates are successively added to the 3 -OH group of the preceding nucleotide, a process that gives the polymer a directional sense. Polymers of ribonucleotides are named ribonucleic acid, or RNA. Deoxyribonucleotide polymers are called deoxyribonucleic acid, or DNA. Because C-1 and C-4 in deoxyribonucleotides are involved in furanose ring formation and because there is no 2 -OH, only... 

A vector for in vitro expression of DNA inserts as RNA transcripts can be constructed by putting a highly efficient promoter adjacent to a versatile cloning site. Figure 13.15 depicts such an expression vector. Linearized recombinant vector DNA is transcribed in vitro using SPG RNA polymerase. Large amounts of RNA product can be obtained in this manner if radioactive ribonucleotides are used as substrates, labeled RNA molecules useful as probes are made. 

FIGURE 18.29 Vitamin B19 functions as a coenzyme in intramolecular rearrangements, reduction of ribonucleotides, and methyl group transfers. 

The first two of these are mediated by 5 -deoxyadenosylcobalamin, whereas methyl transfers are effected by methylcobalamin. The mechanism of ribonucleotide reductase is discussed in Chapter 27. Methyl group transfers that employ tetrahydrofolate as a coenzyme are described later in this chapter. 

MeOQH4CHN2, S11CI2, =50% yield. This method was used to introduce the MPM group at the 2 - and 3 -positions of ribonucleotides without selectivity for either the 2 - or 3 -isomer. The primary 5 -hydroxyl was not affected. 

Galactose, one of the eight essential monosaccharides (Section 25.7), is biosynthesized from UDP-glucose by galactose 4-epimerase, where UDP = uridylyl diphosphate (a ribonucleotide diphosphate Section 28.1). The enzyme requires NAD+ for activity (Section 17.7), but it is not a stoichiometric reactant. and NADH is not a final reaction product. Propose a mechanism. 

Figure 28.1 Structures of the four deoxyribonucleotides and the four ribonucleotides.

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