CHEMICAL STABILITY OF 2′-DEOXY-5-METHYLISOCYTIDINE DURING OLIGODEOXYNUCLEOTIDE SYNTHESIS AND DEPROTECTION

ABSTRACT

Previous studies have encountered difficulties with degradation of some isocytidine derivatives during solid-phase synthesis and deprotection of oligonucleotides. Here we investigate the degradation of a commonly used derivative, 2′-deoxy-5-methylisocytidine, during oligodeoxynucleotide synthesis and deprotection. A small, but detectable amount of hydrolytic deamination occurred at ca. 0.5% of 2′-deoxy-5-methyliso-cytidine residues using routine synthesis and deprotection conditions. Depyrimidination, or cleavage of the glycosylic bond, occurred to a far lesser extent during alkaline deprotection than previously suggested. In contrast to model studies of nucleoside monomers, significant depyrimidination was not observed, even at extended incubation times.

Keywords:

• Isocytosine
• 5-Methyl-2′-deoxycytidine
• Depyrimidination
• Deamination

Acknowledgments