Nucleotide chemistry

The benzyl group has been widely used for the protection of hydroxyl functions in carbohydrate and nucleotide chemistry (C.M. McCloskey, 1957 C.B. Reese, 1965 B.E. Griffin, 1966). A common benzylation procedure involves heating with neat benzyl chloride and strong bases. A milder procedure is the reaction in DMF solution at room temperatiue with the aid of silver oxide (E. Reinefeld, 1971). Benzyl ethers are not affected by hydroxides and are stable towards oxidants (e.g. periodate, lead tetraacetate), LiAIH, amd weak acids. They are, however, readily cleaved in neutral solution at room temperature by palladium-catalyzed bydrogenolysis (S. Tejima, 1963) or by sodium in liquid ammonia or alcohols (E.J. Rcist, 1964). 

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. 

In synthetic work in the phosphorus field, particularly in the realm of nucleotide chemistry, it becomes necessary to remove with ease, from the product (XII), the original R groups so as to produce a true phosphorylation of i OH thus ... 

The intermediate phosphite employed in this synthesis was prepared by condensation of duly protected sialic acid with the nucleosidyl phospho-roamidite in the presence of N-PhIMT. Oxidation by TBHP and deprotection according to standard procedures gave the cytidine-S -monophospho-iST-ace-tylneuraminic acid. This synthetic route is claimed to have advantages over procedures published earlier [26]. The same group demonstrated the importance of 3 A and 4 A molecular sieves as moisture scavengers in the reaction of nucleoside phosphoroamidite with a nucleotide. This approach should be likely to find application in the synthesis of biophosphates outside nucleotide chemistry. 

The overall goal of the proposed work is to broaden our understanding of nucleotide chemistry through gas-phase mass spectrometric and theoretical quantum mechanical studies. The objectives are twofold. First, the gas-phase acidity and nucleophilicity of... 

Nucleotide Chemistry The cells of many eukaryotic organisms have highly specialized systems that specifically repair G-T mismatches in DNA The mismatch is repaired to form a G=C (not A=T) base pair. This G-T mismatch repair mechanism occurs in addition to a more general system that repairs virtually all mismatches. Can you suggest why cells might require a specialized system to repair G-T mismatches ... 

The challenge that Nikolay and his new collaborators faced was even stronger than in some other laboratories, because none of them had a solid background in carbohydrate and nucleotide chemistry. They had to educate themselves, understand the contemporary level of research in these fields, learn the methodology, find their own niche, and only then move forward. All of the staff was enthusiastic and ready to do everything that was needed. Nikolay launched anti-illiteracy seminars in his laboratory where scientific news would be informally discussed once or twice a week, and that proved successful within the year. A professional team, the Kochetkov school , was born. 

The first scientific articles from the IKhPS were submitted for publication in the early 1960s, among them being Nikolay s reports on his work in the new field. His major project in nucleotide chemistry was specific chemical modifications of heterocyclic bases. Reactions of hydroxylamine with cytidine and uridine were studied in detail and a new reagent, O-methylhydroxylamine, was proposed for modification of cytidine. These investigations aimed at the development of efficient methods for sequencing and analysis of the secondary structure of polynucleotides. Later, a reaction of chloroacetaldehyde with adenosine and cytidine was discovered and used for preparation of fluorescent polynucleotide derivatives. 

Regarding the origin of life problem, it remains to determine why this process has been selected by evolution whereas nearly no mixed anhydride is present at equilibrium in the absence of enzyme. If we assume the hypothesis that life emerged from a coevolution process involving both amino acid and nucleotide chemistries, it follows that the translation apparatus must have been formed very early. The only possibility that remains to explain the selection of highly unstable intermediates in peptide biosynthesis is to consider... 

The RNA world hypothesis provides a convenient focus for new experiments that will not only test its validity but will fundamentally advance our knowledge of nucleotide chemistry and RNA catalysis. Several critical experiments should more fully establish (or eliminate) the idea that the forebears of modem life were replicating RNA molecules. 

For the first time, the 1,2,4-oxadiazole ring has been used as a bioisosteres of the ester group in the field of nucleotide chemistry for the production of inhibitors of the bacterial cell-wall synthesis like compound 171.<07JA12642>. 

New Protecting Groups in Nucleoside and Nucleotide Chemistry. Pfleide-rer, W. Schirmeister, H. Reiner, T. Pfister, M. Charubala, R. In Biophosphates and their Analogues—Synthesis, Structure, Metabolism and Activity Bruzik, K. S Stec, W. J., Eds. Elsevier Amsterdam, 1987, pp 133-142. 

DCC is also used in nucleotide chemistry to esterify a sugar hydroxyl group with a phosphate group in another nucleotide or oligonucleotide unit. Also p-styrene based polymers with a pyridyl-2-ethanol end group are reacted in pyridine with 3 -0-acetyl-desoxythimidine-5 -phosphate in the presence of DCC." The reaction of mono esters of phosphoric acid with alcohols or phenols, in the presence of DCC, affords phosphoric acid diesters in high yield." This reaction is widely used in nucleic acid chemistry. 

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