Hoogsteen vs. Watson-Crick base pairing: incorporation of 2-substituted adenine- and 7-deazaadenine 2'-deoxy-beta-D-ribonucleosides into oligonucleotides.
Various 2-substituted 2'-deoxyadenosines and 7-deazaadenosines have been synthesized. The phosphonate building block 9 of 2-chloro-7-deaza-2'-deoxyadenosine (7-deazacladribine; 2) was prepared by 4,4'-dimethoxytritylation of the parent nucleoside (-->7), followed by protection of the amino function with a formamidine residue (-->8). The latter was reacted with PCl3/N-methylmorpholine/1,2,4-triazole to give compound 9. Moreover, 2-methoxy-2'-deoxyadenosine (2'-deoxyspongosine; 1b) was converted into the fully protected derivative 12, which was then transformed into the 2-cyanoethyl phosphoramidite 14. Also the 2-(trifluoromethyl)-substituted 2'-deoxyadenosines 19-21 were prepared by glycosylation of the chromophore 16 with the halogenose 17, followed by one-pot deprotection and nucleophilic displacement of the 6-Cl substituent. The new DNA building blocks 9 and 14 were used--together with formerly prepared cladribine derivative 4--for solid-phase synthesis of a series of oligodeoxyribonucleotides. These were studied with respect to their thermal stability as well as of the base pairing mode (Watson-Crick vs. Hoogsteen) of modified bases.
Ramzaeva
Natalya
N
Organische Chemie I-Bioorganische Chemie, Institut für Chemie, Fachbereich Biologie/Chemie, Universität Osnabrück.
Michalek
Elisabeth
E
Kazimierczuk
Zygmunt
Z
Seela
Frank
F
Rosemeyer
Helmut
H
D000225:Adenine / Q000737:chemistry*; D001372:Aza Compounds / Q000737:chemistry*; D020029:Base Pairing; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D009841:Oligonucleotides / Q000737:chemistry*; D012263:Ribonucleosides / Q000737:chemistry*; D013816:Thermodynamics
D001372:Aza Compounds; D009841:Oligonucleotides; D012263:Ribonucleosides; D000225:Adenine