Bonds intemucleotide

The fundamental problem of oligodeoxyribonucleotide synthesis is the efficient formation of the intemucleotidic phosphodiester bond specifically between C-3 and C-5 positions of two adjacent nucleosides. Any functional group (NH of nucleic base the other OH of deoxy-... 

The IDTr group was developed to protect the 5 -OH of deoxyribonucleotides and to increase the rate of intemucleotide bond formation through participation of... 

Bu4N F , THF, Pyr, H2O, rt, 30 min. These conditions result in the formation of a mixture of fluorophosphate and phosphate. In the case of oligonucleotides, some intemucleotide bond cleavage is observed with this reagent. 

Halogen-substituted phenols were originally introduced for phosphate protection to minimize intemucleotide bond cleavage during deprotection. 

The rate of oligonucleotide synthesis by the triester method using mesitylenesul-fonyl chloride was increased five- to tenfold when this group was used as a protective group during intemucleotide bond formation. It was removed with coned. NH4OH at 60° for 12 h or by the oximate method. ... 

Using method a, oligodeoxyribonucleotides were synthesized from di- to deca-deoxyribonucleotides by means of mesitylenesulfonylimidazole and mesitylenesulfonyl-1,2,4-triazole. With triisoproylbenzenesulfonylimidazole die condensation took place more slowly.11121 Compared widi the corresponding arylsulfonyl chlorides, imidazolides induced intemucleotide condensation much more slowly, but caused no darkening of the reaction mixture, did not affect acid-sensitive bonds in trityl protected nucleotides, and did not sulfonate the 3 -hydroxy groups.11111 The reaction conditions were room temperature, 5—6 days, and pyridine as solvent.11111... 

Imidazolides of adenylic acid (ImpA) or uridylic acid (ImpU) are polycondensed to oligonucleotides by means of Zn2+ ions. 1673 The resulting phosphordiester bond was found to be of the 2, 5 type. In the reaction of nucleoside 5 -phosphoric acid methyl ester with ImpA in the presence of MgC, 2, 5 -dinucleotides are formed six to nine times more frequently than the corresponding 3, 5 compounds. 63 Polycondensations of ImpA in aqueous solution in the presence of various divalent metal ions lead to short oligo-adenylic acids (pA) (n = 1—5) mainly with 2, 5 -intemucleotide linkages. With Pb2+, for example, the total yield of oligomers was as high as 57%. 1683 1693... 

The intemucleotide phosphordiester bonds are composed of both 3, 5 - and 2, 5 -linkages. It was noted that tri(imidazolyl-l)phosphine does not attack the 5 -OH of unprotected uridine. 

By this method, fluorine can be incorporated through a mild procedure into the intemucleotide bond of oligonucleotides. 

Nucleotides are the building blocks of nucleic acids their structures and biochemistry were discussed in chapter 23. When a 5 -phosphomononucleotide is joined by a phosphodiester bond to the 3 -OH group of another mononucleotide, a dinucleotide is formed. The 3 -5 -linked phosphodiester intemucleotide structure of nucleic acids was firmly established by Lord Alexander Todd in 1951. Repetition of this linkage leads to the formation of polydeoxyribonucleotides in DNA or polyribonucleotides in RNA. The structure of a short polydeoxyribonucleotide is shown in figure 25.3. The polymeric structure consists of a sugar phosphate diester backbone with bases attached as distinctive side chains to the sugars. 

Some proteinoids catalyze synthesis of intemucleotide bonds. Adeninedinucleotide is formed from the action of lysine-rich proteinoid with ATP and MgCl2, while a... 

A number of factors combine to lower the susceptibility of phosphoric mono-, di-, and tri-esters to the type of nucleophilic attack required for intemucleotide-bond formation.8 Although a P=0 bond is present, the polarization of this bond is not so great as with an analogous C=0 bond, due to ptt - dn back-bonding into empty, phosphorus d-orbitals.150 Furthermore, the pKa values for the first dissociations of both phosphoric mono- and di-esters are approximately unity,8 which means that, in reactions in pyridine, the anions are involved. Partial delocalization of the formal, negative charge into phosphorus... 

As a similar protecting function the 1-ethoxyethyl ether, formed by reaction of the alcohol with ethyl vinyl ether, was introduced (Scheme 28). It displayed advantageous properties for the construction of oligonucleotides since it could be cleaved with 5% acetic acid without affecting the intemucleotide bond. ... 

Khorana found this an eiiicient reagent for the synthesis of the intemucleotide < bond. When the protected nucleotide (1) and the protected nucleoside (2)... 

An approach to the stereospecific, solid phase synthesis of methylphosphonates has been developed whereby an appropriately protected, stereochemically pure J p or 5p 3 -(p-nitrophenyl methylphosphonate) ester (65) is coupled to an activated S -hydroxyl group of a support-bound nucleoside. The 5 -hydroxyl group is activated by the addition of a Grignard reagent in pyridine and the release of p-nitrophenol is accompanied by stereospecific intemucleotide bond... 

A new method for intemucleotide bond formation uses a transesterification reaction in pyridine of the aryl nucleoside /f-phosphonate diesters (76) with a... 

Later MD studies on DNA triplexes were often devoted to the stability and the H-bond pattern of the base triads, to the conformational properties of the sugar-phosphate backbone, to the effect of modified nucleotides and to the hydration pattern. Modified nucleotides include structures derived from 2-aminopyridine and 8-aminoguanine a triplex with the phosphodiester linkage in two strands replaced by S-methylthiourea linkers, 2 -aminoethoxy-substituted riboses and a -CH2-lengthening of the intemucleotide linkage. ... 

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