Enhanced i-Motif Stability through Consecutive 2',2'-Difluorocytidine Incorporation.

ABSTRACT: Chemical modifications of nucleic acids are widely used to tune stability and functionality in therapeutic and nanotechnological applications. Among these, fluorinated cytidine derivatives such as 2'-fluoro-arabinocytidine (2'F-araC) and 2'-fluoro-ribocytidine (2'F-riboC) have been shown to influence i-motif structures differently, with 2'F-araC strongly stabilizing and 2'F-riboC exerting a mildly deleterious effect. In this study, we investigate the impact of gemcitabine (2'-deoxy-2',2'-difluorocytidine, dFdC) on i-motif stability. dFdC exhibits small effects in single or double substituted sequences, but a pronounced stabilization when multiple consecutive residues are incorporated. Thermal and pH-dependent analyses demonstrate that sequences containing fully substituted dFdC maintain i-

SUBMITTER: Dominguez A 

PROVIDER: S-EPMC12734662 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature