Nucleic acid derivatives antibiotics

Some of the substances that have been separated by this method are given in papers referred to by Morris and Morris (1964) amino acids, peptides (particularly those having molecular weights ranging from 500 to 5000), polypeptide antibiotics, proteins (including enzymes), carbohydrates (although for most compounds in this chemical class other fractionation methods are much more frequently applied), purines, pyrimidines, nucleic acid derivatives, tRNA s that are specific for various amino acids, organic acids, steroids, lipids, antibiotics that are not peptides, porphyrins, pterins, vitamin B,2 and other vitamins, lipoic acid, and alkaloids. The countercurrent-distribution procedure of Holley et al. (1965) is widely used, sometimes with modifications. Korte et al. (1965) have separated three isomers of tetrahydrocannabinol. 

A number of 1,2,4-triazines are of interest owing to their biological activity. 1,2,4-Triazine-3,5-diones (6) represent aza analogues of pyrimidine nucleic acid bases, a number of natural antibiotics are derivatives of pyrimido[5,4-e][l,2,4]triazine (7), and 4-amino-6-r-butyl-3-methylthio-l,2,4-triazin-5-one (8) and 4-amino-3-methyl-6-phenyl-l,2,4-triazin-5-one (9) are used as herbicides. 

In comparison with the penicillin and cephalosporin derivatives, the peptide antibiotics are not numbered among the major antibiotics . Their action mechanisms vary, e.g. inhibition of cell-wall synthesis, increased permeability of the cell wall, or influence on nucleic acid synthesis. 

Figure 3.14 Structures of common nucleosides whose acid-catalysed hydrolysis has been studied. Adenosine, guanosine and cytidine are three of the four common nucleosides in RNA and their 2 -deoxy derivatives in DNA, whereas uridine is found only in RNA and 2 -deox5hh5midine in DNA. Psicofuranine is an antibiotic and is not a common constituent of nucleic acids. Inosine is a commonly used substrate in investigations of enzymic ribosyl transfer.

Celluloses Amines, amino acids, antibiotics, carbohydrates, glycosides, hydrocarbons, inorganic ions, nucleic acids, organic acids, peptides, urea derivatives, vitamins... 

Complex of glycopeptide antibiotics related to Bleomycins. Derived from Streptomyces verticillus. Active against gram-positive and -negative bacteria and tumours, inhibitor of nucleic acid synth. A complex mixt. of amines Phleomycins A, C, D, D2, E, F, G and H derived by directed biosynth. or semisynth. See also Bleomycins. X , 245 (e 23600) 296 (e 19600) (HjO) (Derep). 244 (e 24500) 298 (e 8300) 615 (e 100) (MeO (Berdy). 

As early as 1951, affinity chromatography was used for the separation of anti-hapten antibodies (Campbell et aL, 1951). Shortly afterwards, Lerman (1953) developed a similar method for purification of tyrosinase. The recent applications of affinity chromatography are too numerous to be detailed here, but broadly speaking, the method has been used for separation/purification of proteins, sugars and their derivatives, nucleic acids, nucleotides and their derivatives, amino acids and peptides, and various other systems that include thiols and disulfides (ligands-thiols or disulfides or organomercurial supports), steroidal hormones, coenzymes, vitamins, morphine and related drugs, antibiotics, protein receptors, and antibodies. 

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. 

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