Oligonucleotide Analogues with Integrated Bases and Backbone (ONIB) Part 31~1) Aminomethylene-Linked CG and GC Dinucleosides of the ONIB Type: Formation of Duplexes and Quadruplexes

摘要

The self-complementary guanosine- and cytidine-derived aminomethylene-linked C~*[n]G dinucleoside 9 was synthesized by reductive amination of aldehyde 3 with an iminophosphorane derived from azide 7. Deacylation of 9 gave the isopropylidene-protected dinucleoside 10. The sequence-isomeric G~*[n]C dinucleoside 11 was similarly prepared from aldehyde 8 and azide 5, and deacylated to 12. The association of 10 and 12 in CHCl_3 or in CHCl_3/DMSO mixtures, and the structure of the associates were studied by ~1H-NMR, ESI-MS, CD, and vapor pressure osmometry (VPO). Broad ~1H-NMR signals of dinucleosides 10 and 12 evidence an equilibrium between duplexes and quadruplexes (Hoogsteen base pairing between the Watson-Crick base-paired duplexes). The quadruplex dominates for the G~*[n]C dinucleoside 12 between -50° and room temperature. The sequence-isomeric C~*[n]G 10 forms mostly only a cyclic duplex in CDCl_3 and in CDCl_3/(D_6)DMSO 9:1.