Synthesis and duplex DNA recognition studies of oligonucleotides containing a ureido isoindolin-1-one homo- N-nucleoside. A comparison of host–guest and DNA recognition studies

Abstract

In an effort to construct non-natural bases to be used in triplex-based antigene DNA recognition strategies, a uriedo-isoindolin-1-one homo- N-nucleoside base was designed to bind the cytosine-guanine (CG) base pair. An organic soluble analogue of this base was shown to effectively complex CG (K assoc=740 M −1) in chloroform through formation of three hydrogen bonds (Mertz, E.; Mattei, S.; Zimmerman, S. C. Org. Lett. 2000, 2, 2931–2934). The novel nucleoside base was synthesized and successfully incorporated into oligonucleotides which were used in triple helix melting temperature studies. Low melting temperatures were observed when the isoindolin-1-one base was paired opposite CG as well as GC, TA, and AT, thus indicating that despite favorable recognition in model studies, the artificial base did not effectively recognize duplex DNA to form pyrimidine-purine-pyrimidine type triple helices.