Uracil 6 - amino -1 - - 5 methyl

Folic acid derivatives are essential for DNA synthesis, in that they are cofactors for certain reactions in purine and pyrimidine biosynthesis, including the uracil-thymine methylation just described. They are also cofactors for several reactions relating to amino acid metabolism. The folic acid system thus offers considerable scope for drug action. 

Fujita S, Steenken S (1981) Pattern ofOFI radical addition to uracil and methyl-and carboxyl-substituted uracils. Electron transfer ofOFI adducts with N,N, Ar, Ar -tetramethyl-p-phenylenediamine and tetranitromethane. J Am Chem Soc 103 2540-2545 Fujita S, Nagata Y, Dohmaru T (1988) Radicals produced by the reactions of SO4 with uridine and its derivatives. Studies by pulse radiolysis and y-radiolysis. Int J Radiat Biol 54 417-427 Fujita S, Horii FI,Taniguchi R, Lakshmi S, Renganathan R (1996) Pulse radiolytic investigations on the reaction of the 6-yl radicals of the uracils with Cu(ll)-amino acid complexes. Radiat Phys Chem 48 643-649... 

All bases found in nucleic acids are derivatives of purine or pyridine. Only in some nucleoside antibiotics is an exchange of a carbon atom for a nitrogen atom, or vice versa, observed. The common bases are adenine 6-amino-purine guanine 2-amino-6-ketopurine cytosine 2-keto-4-aminopyrimidine uracil 2,4-diketopyrimidine and thymine (in DNA) 2,4-diketo-5-methylpyrimidine (5-methyluracil). Minor components found in various DNA and RNA are 5-methylcy-tosine, 5-hydroxymethylcytosine, 5-hydroxymethyluracil, 6-methylaminopurine, 5,6-dihydrouracil (in tRNA) and numerous other methylated bases (in tRNA). The bases are quite resistant to oxidation but easily attacked by nucleophilic reagents. In particular, the positions meta to the nitrogen atoms have low electron densities. Substitutions by electron donors (amino, methyl, hydroxyl) facilitate nucleophilic substitution on the other atoms. 

Figure 12 Gradient separation of bases, nucleosides and nucleoside mono- and polyphosphates. Column 0.6 x 45 cm. Aminex A-14 (20 3 p) in the chloride form. Eluent 0.1 M 2-methyl-2-amino-l-propanol delivered in a gradient from pH 9.9-100 mM NaCl to pH 10.0-400 mM NaCl. Flow rate 100 ml/hr. Temperature 55°C. Detection UV at 254 nm. Abbreviations (Cyt) cytosine, (Cyd) cytidine, (Ado) adenosine, (Urd) uridine, (Thyd) thymidine, (Ura) uracil, (CMP) cytidine monophosphate, (Gua) guanine, (Guo) guanosine, (Xan) xanthine, (Hyp) hypoxanthine, (Ino) inosine, (Ade) adenosine, (UMP) uridine monophosphate, (CDP) cytidine diphosphate, (AMP) adenosine monophosphate, (GMP) guanosine monophosphate, (IMP) inosine monophosphate, (CTP) cytidine triphosphate, (ADP) adenosine diphosphate, (UDP) uridine monophosphate, (GDP) guanosine diphosphate, (UTP) uridine triphosphate, (ATP) adenosine triphosphate, (GTP), guanosine triphosphate. (Reproduced with permission of Elsevier Science from Floridi, A., Palmerini, C. A., and Fini, C., /. Chromatogr., 138, 203, 1977.)...

Thymine derivatives - 5-[7V-(2-Amino-4-hydroxy-6-methyl-5-pyrimidinyl-propyl)-p-carboxyanilinomethyl] uracil (XXXIII) was synthesized for study as a possible intermediate in the enzymatic synthesis of thymidylate. It is active as an enzyme inhibitor against thymidylate synthetase isolated from E. coli [298]. Certain thymine derivatives containing a 2-thioimidazole moiety (XXXIV, R = alkyl) inhibit growth of Ehrlich ascites carcinoma (fluid form) in mice [299]. 

Treatment of certain uracils, such as l-methyl-6-amino-,3-methyl-6-amino- or 1,3-dimethyl-5,6-diaminouracil with formaldehyde gave compounds containing between 10—30 per cent by weight of reversibly bonded formaldehyde. These new compounds were claimed to be useful as disinfectants or antiseptics [413]. 

OCH3, SH, NH2, CHg, or COOH,205 adenine-thymine base pair171,175,184, 185 and its cationic and anionic forms209 (for the charge densities at C-5 and C-6 positions in uracil, thymine, 5-amino- 5-nitro- and 6-methyl-uracil, 6-azathymine and orotic acid, see refs. 187, 188) it-HMO + a-Del Re calculations on uracil,369,397 5-fluoro- and 5-bromouracil,397 5,6-dihydrouracil and its anionic form369 n-SCF MO + a-Del Re... 

Substitution of the aromatic C(5)H in uracil by a methyl group (to give thymine) decreases the acidity of N(3)H by 0.5 log units (cf. Table I). Replacement of protons of endocyclic N atoms and of exocyclic amino groups by alkyl groups in general has a relatively minor effect on the pkl, values of nucleobases. For example, the pvalues of N1 protonated 9-methyladenine (9-MeA), 6,9-dimethyladenine (6,9-DiMeA), and 6,6,9-trimethyladenine (6,6,9-TriMeA) are... 

L of 10% NaOH solution was slowly added to 2.9 kg (11.8 mole) of crude l-methyl-l-cyanoacetyl-3-(2-methyl-l-butyl)urea with stirring. The oil dissolved and shortly another oil precipitated. The temperature rose to about 60°C and then dropped. After stirring for a while at room temperature the oil crystallized. After cooling the product was filtered. The crude product was slurred in water and dried at 50°C in vacuum to yield 2.1 kg of 4-amino-l-methyl-3-(2-methyl-l-butyl)uracil. MP 121-124°C. Yield 85%. 

Amino-5-nitroso-l-methyl-3-(2-methyl-l-butyl)uracil ... 

L of cone, ammonium hydroxide (58%) was added to 1.9 kg (7.9 mole) of 4-amino-5-nitroso-l-methyl-3-(2-methyl-l-butyl)uracil. An orange salt formed. The suspension was placed in an oil bath at 80-90°C and a solution resulted. 5.6 kg (32.3 mole) of sodium dithionite was added in portions over about 30 min. When the addition was complete stirring was continued for 30 min. The reaction was allowed to cool to room temperature and stirred overnight. After cooling the precipitate was filtered, slurred with water and dried at 80°C in vacuum to yield 1.25 kg of 4,5-diamino-l-methyl-3-(2-methyl-l-butyl)uracil. MP 161-163°C. Yield 70%. 

The replacement of thymine by uracil has no significant effect on the hydrogen bonding, as RNA does not use base pairing to form complementary dimers it is of less importance than it would be for DNA, but the removal of the methyl group may have an influence on the tertiary structures that RNA can adopt. From this it is clear that DNA is a better method of storing information whereas RNA is more suited to turn that information into a protein sequence. This is done by the ribosome, composed of ribosomal RNA (rRNA), which translates the codons of the mRNA sequence into a protein by matching three base sequences to those of tRNA that have the appropriate amino acids attached. 

Transfer RNA (Mr s= 25,000) functions as an adapter in polypeptide chain synthesis. It comprises 10-20 percent of the total RNA in a cell, and there is at least one type of tRNA for each type of amino acid. Transfer RNAs are unique in that they contain a relatively high proportion of nucleosides of unusual structure (e.g., pseudouridine, inosine, and 2 -0-methylnucleosides) and many types of modified bases (e.g., methylated or acetylated adenine, cytosine, guanine, and uracil). As examples, the structures of pseudouridine and inosine are shown below. Inosine has an important role in codon-anticodon pairing (Chap. 17). 

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