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Synthesis and Pairing Properties of Oligodeoxynucleotides Containing N 7 ‐(Purin‐2‐amine Deoxynucleosides)
Author(s) -
Parel Serge P.,
Leumann Christian J.
Publication year - 2000
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(20000906)83:9<2514::aid-hlca2514>3.0.co;2-x
Subject(s) - chemistry , guanine , amine gas treating , base pair , phosphoramidite , stereochemistry , nucleotide , nucleobase , dna , base (topology) , selectivity , nucleoside , oligonucleotide , deoxyribonucleotide , organic chemistry , biochemistry , mathematical analysis , mathematics , gene , catalysis
A general synthesis of the four isomeric N 7 ‐ α ‐ D ‐, N 7 ‐ β ‐ D ‐, N 9 ‐ α ‐ D ‐, and N 9 ‐ β ‐ D ‐(purin‐2‐amine deoxynucleoside phosphoramidite) building blocks for DNA synthesis is described ( Scheme ). The syntheses start with methyl 3′,5′‐di‐ O ‐acetyl‐2′‐deoxy‐ D ‐ribofuranoside ( 2 ) as the sugar component and the N 2 ‐acetyl‐protected 6‐chloropurin‐2‐amine 1 as the base precursor. N 7 ‐Selectivity was achieved by kinetic control, and N 9 ‐selectivity by thermodynamic control of the nucleosidation reaction. The two N 7 ‐(purin‐2‐amine deoxynucleosides) were introduced into the center of a decamer DNA duplex, and their pairing preferences were analyzed by UV‐melting curves. Both the N 7 ‐ α ‐ D ‐ and N 7 ‐ β ‐ D ‐(purin‐2‐amine nucleotide) units preferentially pair with a guanine base within the Watson‐Crick pairing regime, with Δ T m s of −6.7 and −8.7 K, respectively, relative to a C⋅G base pair ( Fig. 3 and Table 1 ). Molecular modeling suggests that, in the former base pair, the purinamine base is rotated into the syn ‐arrangement and is able to form three H‐bonds with O(6), N(1), and NH 2 of guanine, whereas in the latter base pair, both bases are in the anti ‐arrangement with two H‐bonds between the N(3) and NH 2 of guanine, and NH 2 and N(1) of the purin‐2‐amine base ( Fig. 4 ).