Base-pairing properties

All of the hybridization procedures discussed in this section depend on the specific base-pairing properties of complementary nucleic acid strands described above. Perfect matches hybridize readily and withstand high temperatures in the hybridization and washing reac-... 

Self complementary mesomeric betaines of guanine obtained from guanine IV-oxide have been described and their base pairing properties studied <02CL222>. The stereoselective reaction of adenine with methylglyoxal, in water, under mild conditions, afforded a new family of heterocycles, and can be used for understanding the biological effects of... 

The phosphoramidite derivative of N-nitrothymidine (44) has been synthesised and found suitable for oligonucleotide synthesis using a standard phosphite triester solid phase approach. The N-nitrothymidine residues could be converted into a range of N -modified thymidines by reaction with primary alkyl amines. Phosphoramidite derivatives of 4-nitroindazole N and N -(2 -deoxy-p-D-ribofuranosides) (45, 46) have been synthesised, their base pairing properties investigated and found to show ambiguous base pairing. Seela has also reported the syntheses of the phosphoramidite derivatives of 8-aza-7-adenine... 

The base pairing properties of the a- and p-anomers of the imidazo[l,2-a]-1,3,5-triazine nucleoside (96) have been described. Both anomers are more stable than duplexes with dG, though the a-anomer is most stable. When the p-anomer alternates with dG, antiparallel duplexes (aps) are observed, but parallel duplexes (ps) are formed with the a-anomer. A reversal of the chain orientation (ps- aps) occurs when the P-anomer pairs with 2 -deoxyisoguanosine. 

Due to the steric constraints of Watson-Crick base pairing, modifications of bases, which do not negatively affect base pairing properties are possible only to a limited extent. Some modifications are shown in Table 9. 

Base modification at the 4-position of pyrimidines leads to loss of base-pairing properties. The thiol moiety in 91 was deprotected after ODN synthesis using 1 M DBU in acetonitrile. The modified oligothymidylate was then cleaved from the solid phase and reacted with N-(2-chloroethylthio)phthalimide to yield 92, which was subjected to further derivatization [264]. Purine base positions accessible for ligand attachment are C-8 of adenosine (93) [265] and C-2 of guanosine (94) [266]. 

A further option is given by application of bases with inexact base-pairing properties. Due to tautomeric structures, nucleobase P forms hydrogen bridges with adenine and guanine, and nucleobase K with cytidine and thymine (Fig. 34). Thus, a mixture of phosphorami-dites P and K may be used at positions of unknown bases instead of the mixture of the phor-phoramidites dA, dG, dT, dC. 

Wu X, Pitsch S. Synthesis and base-pairing properties of oligoribonucleotide analogues containing a metal-binding site attached to jS-D-allofuranosyl cy-tidine. Nucleic Acids Res 26 4315-4323, 1998. 

The significant structural results which have been discussed here are summarized in Figure 11. All, in the absence of intermolecular solid state effects, fall in a narrow torsional range centered near x= 100° which is quite different from that found in the natural systems. It is apparent that incorporation of a nucleoside in this conformation into a polynucleotide could have dramatic effects on the coding and base-pairing properties of the nucleic acids. Such a result could explain the observation that replacement of a natural pyrimidine nucleoside in the valine codon by 6-AUD or 6-ACD results in a nonfunctional unit [3], and could also explain the anti-neoplastic properties of these and similar molecules. 

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