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Synthesis and Hybridization Ability of Oligodeoxyribonucleotides Incorporating N ‐Acyldeoxycytidine Derivatives
Author(s) -
Wada Takeshi,
Kobori Akio,
Kawahara Shunichi,
Sekine Mitsuo
Publication year - 2001
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200112)2001:24<4583::aid-ejoc4583>3.0.co;2-r
Subject(s) - chemistry , intramolecular force , hydrogen bond , stereochemistry , oligonucleotide , guanine , base pair , amide , molecule , dna , ab initio , methylene , nucleobase , crystallography , organic chemistry , nucleotide , gene , biochemistry
Oligodeoxynucleotides [ 11a−i : d(T 6 XT 6 )] incorporating various N ‐acyldeoxycytidine derivatives (X) have been synthesized through use of a new DBU‐labile 4,5‐dichlorophthaloyl linker on polymer supports. The hybridization capabilities of these oligonucleotides with the complementary d(A 6 GA 6 ) were examined with the aid of T m experiments. It turned out that the T m values of DNA duplexes decreased significantly with an increase in the number of the methylene groups in the aliphatic acyl group introduced into one strand of the DNA duplex. Ab initio MO calculations and 1 H NMR analysis suggested that the acyl groups in the tested derivatives were oriented in a manner that made the formation of conventional Watson−Crick‐type (W−C‐type) base pairs with the guanine residue possible, with the help of an intramolecular hydrogen bond between the amide carbonyl oxygen atom and the 5‐vinyl proton of the N ‐acylcytosine residue. Moreover, all the aromatic N ‐acyl groups were found markedly to decrease the thermal stability of the DNA duplexes. Ab initio calculations suggested that the base pairs formed between 4‐ N ‐acyl‐1‐methylcytosine derivatives and 9‐methylguanine have wholly planar structures as their most stable geometries. Detailed studies of the hydrogen‐bond energy of the modified base pairs also suggested that the electronic repulsion between the heteroatom of the acyl group of X and the guanine residue resulted in significant destabilization of the X‐G base pair and that the hydrogen‐bond network structure of water molecules around the major groove of the DNA duplex is a key factor in the stabilization of DNA duplexes.