Inosinic acid, structure

The 5 -nucleotide of inosine, inosinic acid (C10H13N4O8P) is added to foods as a flavor enhancer. What is the structure of inosinic acid (The structure of inosine is given in Problem 28.21). 

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. 

Phosphorylation of XLVII with phosphorus oxychloride in pyridine solution, followed by hydrolysis to remove the methyl and isopropylidene residues, gave D-ribose 5-phosphate (XLVIII) which, as its barium salt, was found to be identical with the barium salt of the D-ribose phosphate from inosinic acid. By way of further confirmation of the structure of D-ribose 5-phosphate, Levene, Harris and Stiller129 showed that in methanolic hydrogen chloride solution both the natural and synthetic material mutarotated in a manner characteristic of a sugar which can form only a furanoside. 

Historically, this method of stepwise hydrolysis seems to have been first applied to a nucleotide by Levene and Jacobs, in determining the structure of muscle inosinic acid. ... 

Finally, muscle inosinic acid itself was synthesized by Levene and Tipson. This was the first (partial) synthesis of a naturally occurring nucleotide. Phosphorylation of 2,3-isopropylidene-inosine, the structure of which has already been discussed, gave the corresponding 5-phospho derivative, from which the isopropylidene group was cautiously hydrolyzed, yielding 5-phosphoinosine which proved to be identical with muscle inosinic acid. 

In 1925, the structure of inosinic acid, which was thought to be the 5 -monophosphate of inosine, was confirmed. Inosinic acid, the first free nucleotide to be recognized, has an interesting history (4). In 1847, the barium salt of this substance was isolated from beef extract by Leibig, who derived the name from the Greek words for muscle fiber. The presence of phosphorus in this substance was not recognized until 1895. In 1909, Levene determined the structure of inosine, a hydrolysis product of inosinic acid, to be the riboside of hypoxanthine with this information, the nucleotide structure of inosinic acid became apparent. 

The purine bases, adenine and guanine, participate in nature by providing structural elements of nucleic acids and numerous cofactors. The deaminated products of adenine and guanine do not participate in these coenzymic functions except in a relatively few instances. For example, the relative ineffectiveness of inosine monophosphate (IMP) vs. 

This contribution complements an earlier review (11) which summarized our NMR research on synthetic DNA s and RNA s with alternating inosine-cytidine and guanosine-cytidine polynucleotides and the structure and dynamics of ethidium-nucleic acid complexes. 

Kalckar117118119 has shown that the enzymatic phosphorolysis of inosine (hypoxanthine 9-D-ribofuranoside) may give rise to the formation of a pentose phosphate, isolable as its barium salt. The phosphate was found to be non-reducing although easily hydrolyzed by either acid or alkali to equimolar quantities of phosphate and pentose. In view of these properties and the fact that it could be used for the enzymatic synthesis of purine ribosides, Kalckar has tentatively assigned to it the D-ribose 1-phosphate structure its ring structure and configuration at carbon 1 remain undetermined. 

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). 

In inosine monophosphate dehydrogenase, the monovalent metal ion accelerates the hydride transfer step of the reaction with apparently few other effects on the enzyme structure. Probably the monovalent cation is involved in helping position the nicotinamide cofactor. The active site and location of the potassium ion are shown in Figure 2. Mycophenolic acid in this diagram is an inhibitor that is thought to lock inosine monophosphate into the active site, as shown. Note the large distance between the inhibitor (in the active site) and the K+. 

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