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Oligonucleotide Analogues with Integrated Bases and Backbone. Part 22
Author(s) -
Bernet Bruno,
Johar Zeena,
Ritter Anne,
Jaun Bernhard,
Vasella Andrea
Publication year - 2009
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/hlca.200900203
Subject(s) - chemistry , nucleobase , base pair , stereochemistry , crystallography , antiparallel (mathematics) , oligonucleotide , nucleoside , dna , biochemistry , physics , quantum mechanics , magnetic field
The tritylated and silylated self‐complementary A*[s]U*[s]A*[s]U* and U*[s]A*[s]U*[s]A* tetramers 18 and 24 , linked by thiomethylene groups (abbreviated as [s]) between a nucleobase and C(5′) of the neighbouring nucleoside unit were prepared by a linear synthesis based on S ‐alkylation of 5′‐thionucleosides by 6‐(chloromethyl)uridines, 7 or 10 , or 8‐(chloromethyl)adenosines, 12 or 15 . The tetramers 18 and 24 were detritylated to the monoalcohols 19 and 25 , and these were desilylated to the diols 20 and 26 , respectively. The association of the tetramers 18 – 21 and 24 – 26 in CDCl 3 or in CDCl 3 /(D 6 )DMSO 95 : 5 was investigated by the concentration dependence of the chemical shifts for HN(3) or H 2 NC(6). The formation of cyclic duplexes connected by four base pairs is favoured by the presence of one and especially of two OH groups. The diol 20 with the AUAU sequence prefers reverse‐ Hoogsteen , and diol 26 with the UAUA sequence Watson–Crick base pairing. The structure of the cyclic duplex of 26 in CDCl 3 at 2° was derived by a combination of AMBER* modeling and simulated annealing with NMR‐derived distance and torsion‐angle restraints resulting in a Watson–Crick base‐paired right‐handed antiparallel helix showing large roll angles, especially between the centre base pairs, leading to a bent helix axis.