Nucleobase–Guanidiniocarbonyl-Pyrrole Conjugates as Novel Fluorimetric Sensors for Single Stranded RNA

We demonstrate here for the first time that a guanidiniocarbonyl-pyrrole (GCP) unit can be applied for the fine recognition of single stranded RNA sequences—an intuitively unexpected result since so far binding of the GCP unit to ds-DNA or ds-RNA relied strongly on minor or major groove interactions, as shown in previous work. Two novel nucleobase–GCP isosteric conjugates differing in the flexibility of GCP unit revealed a fluorimetric recognition of various single stranded RNA, which could be additionally regulated by pH. The more rigid conjugate showed a specific fluorescence increase for poly A only at pH 7, whereby this response could be reversibly switched-off at pH 5. The more flexible derivative revealed selective fluorescence quenching by poly G at pH 7 but no change for poly A, whereas its recognition of poly AH(+) can be switched-on at pH 5. The computational analysis confirmed the important role of the GCP fragment and its protonation states in the sensing of polynucleotides and revealed that it is affected by the intrinsic dynamical features of conjugates themselves. Both conjugates showed a negligible response to uracil and cytosine ss-RNA as well as ds-RNA at pH 7, and only weak interactions with ds-DNA. Thus, nucleobase–GCP conjugates can be considered as novel lead compounds for the design of ss-RNA or ss-DNA selective fluorimetric probes.