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Screening the structural space of bicyclo-DNA: synthesis and properties of bicyclo-DNA functionalized at C(6')

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2010
Author Luisier S., Leumann C. J.,
Project Chemically modified Oligonucleotides for Biotechnology and Material Sciences
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Original article (peer-reviewed)

Journal Heterocycles
Volume (Issue) 82
Page(s) 775 - 790
Title of proceedings Heterocycles


The synthesis of a novel bicyclo-thymidine nucleoside bearing an ester functionality at C(6') (bc(alpha-alk)-nucleosides) is reported. This nucleoside was incorporated into oligodeoxynucleotides via solid phase phosphoramidite chemistry, and the ester moiety was post-synthetically converted to an amide or a carboxy group, or was left unchanged. Thermal melting data (T-m) with complementary DNA and RNA were collected and compared to natural DNA and to bc- and bc(ox)-DNA. It was found that single incorporations of bc(alpha-alk)-nucleosides in DNA duplexes were destabilizing by 0.5 to 2.5 degrees C/mod, whereas two consecutive bc(alpha-alk)-residues were less destabilizing, and in some cases even stabilizing by 0.5 degrees C/mod. In duplexes with complementary RNA, isolated bc(alpha-alk)-residues destabilized the duplex by -1.0 to -4.0 degrees C/mod, depending on the chemical nature of the substituent, whereas two consecutive modifications were only destabilizing by 0.3-1.0 degrees C/mod. The pairing selectivity was similar to that of unmodified or bc-DNA.