Oligonucleotide Analogues with Integrated Bases and Backbones. Part 26 : Synthesis, Conformational Analysis, and Association of Aminomethylene-Linked Self-Complementary Adenosine and Uridine Dinucleosides with Enforced syn-Conformation

✍ Scribed by Katja Chiesa; Bruno Bernet; Andrea Vasella

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: German
• Weight: 430 KB
• Volume: 93
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.201000217

✦ Synopsis

Abstract

The self‐complementary aminomethylene‐linked A*[n]U* dinucleosides 23–26 were prepared by reductive coupling of aldehyde 10 and azide 8. The U*[n]A* sequence isomers 19–21 were similarly prepared from aldehyde 14 and azide 3. The substituents at C(6/I) of 23–26 and at C(8/I) of 19–21 strongly favour the syn‐conformation. The A*[n]U* dinucleoside 23 associates more strongly than the sequence‐isomeric U*[n]A* dinucleoside 19. The A*[n]U* dinucleosides 23 and 24 associate more strongly than the analogues devoid of the substituent at C(6/I), while the U*[n]A* dinucleoside 19 associates less strongly than the analogue devoid of the substituent at C(8/I). While 23 and 24 form cyclic duplexes mostly by Watson–Crick‐type base pairing, 25 only forms linear associates. The U*[n]A* dinucleoside 19 forms mostly linear duplexes and higher associates, and 21 forms cyclic duplexes showing both Watson–Crick‐ and Hoogsteen‐type base pairing. The cyclic duplexes of the aminomethylene‐linked dinucleosides show both the gg‐ and gt‐orientation of the linker, with the gg‐orientation being preferred.