1,3-Azolecarboxamide nucleobase analogs: Design, synthesis, and thermo dynamic studies

1,3-Azolecarboxamides are an unusual family of nucleobase analogs whose members can hypothetic-ally assume hydrogen bond donor and acceptor group configurations which closely resemble those of the natural nucleobases. Within this family are molecules that can be superimposed onto bofh pyrimidine and purine nucleobases by conformational and lautomeric transformations, which suggests that there may be individual members capable of functioning as two or more natural bases. Research is underway to determine how well selected members of the 1,3-azoIecarboxamide family base pair to each of the four nat ural nucleobases within a ONA duplex. The deoxyribosyl derivatives of the analogs were synthesized from pyrrole, pyrazole, imidazole and triazole esters. and subsequently transformed to the deoxyribosyl azolecarboxamides by known synthetic methods. NMR titration experiments to measure hydrogen bonding to the natural bases have been done with bis-triisopropylsüyl derivatives. Con version to the, V-protected dimethoxytrityl 31 phosphoramidites allowed incorporation of the nucleobase analogs into oligodeoxyribonucleotides. Thermal denaturation studies on the oligonucleotide sequence 5′ d(CGCXAATTYGCC.) 3 where X is the deoxyribosyl azolecarboxamide and Y is one of the four natural bases, show that members of the 1,3-azolecarboxamide family are able to behave as ambidextrous base paring partners.