Novel heterocyclic nucleosides as components of DNA
Abstract
A series of unique heterocyclic nucleoside analogues were synthesized and incorporated into oligodoexyribonucleotides by solid-phase phosphoramidite methodology. Four self-complementary oligodeoxyribonucleotide sequences were synthesized for each modified nucleoside in order to obtain DNA duplexes with either of the four naturally occurring nucleobases (A, C, G, or T) situated opposite each modified nucleobase. Unmodified oligodeoxyribonucleotides and oligodeoxyribonucleotides containing several previously studied modified nucleobase moieties were also synthesized. Thermal melting studies were performed on the DNA duplexes in order to assess the ability of each modified nucleoside to function as a component of DNA. A conformationally flexible nucleoside analogue, 1-(2$\sp\prime$-deoxy-$\beta$-D-ribofuranosyl)imidazole-4-carboxamide (J5), was found to mimic dA in the relative order of its base pairing preferences (T $>$ dG $>$ dA $>$ dC). However, J5 was less discriminate than dA in its bias for pairing with T over dG. 1-(2$\sp\prime$-Deoxy-$\beta$-D-ribofuranosyl)-3-nitropyrrole (Z1) was found to be the least discriminate nucleoside analogue that was utilized in this study. The T$\sb{\rm m}$ values of a group DNA duplexes containing Z1 differed by just five degrees. Likewise, 1-(2$\sp\prime$-deoxy-$\beta$-D-ribofuranosyl)-4-bromopyrazole (J3) also formed very nonspecific base pairs with each of the standard nucleobases. In contrast, base pairs between 1-(2$\sp\prime$-deoxy-$\beta$-D-ribofuranosyl)-4-nitropyrazole (J1) or 1-(2$\sp\prime$-deoxy-$\beta$-D-ribofuranosyl)-4-nitroimidazole (J2) and each of the standard nucleobases were more specific. Nucleoside J1 showed a slight preference for pairing with dA while nucleoside J2 was highly selective in its preference for base pairing with dG.
Degree
Ph.D.
Advisors
Bergstrom, Purdue University.
Subject Area
Molecular biology|Organic chemistry|Pharmacology|Biochemistry
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