Formaldehyde (FA) is endogenously produced in living systems through a variety of biological processes and has been implicated in many pathological conditions. Detection tools for biological FA are therefore of great interest. Reported here are novel activity‐based genetically encoded fluorescent and luminescent probes for detecting FA in aqueous solutions and living mammalian cells. A FA‐reactive lysine analogue, PrAK, was site‐specifically incorporated into the essential lysine sites of enhanced green fluorescent protein (EGFP) and firefly luciferase (fLuc) to afford fluorescent and luminescent FA probes, respectively. FA selectively reacts with PrAK residues on EGFP and fLuc through a 2‐aza‐Cope rearrangement, resulting in fluorescence and luminescence turn‐on responses, respectively, to FA selectively over potentially interfering reactive species in aqueous buffer. Moreover, the genetically encoded probes are capable of visualizing FA at physiologically relevant levels in living mammalian cells by fluorescence and luminescence imaging, demonstrating their potential as new tools to explore FA biology.

Protein S-palmitoylation, or S-fatty-acylation, regulates many fundamental cellular processes in eukaryotes. Herein, we present a chemical fatty-acylation approach that involves site-specific incorporation of cycloalkyne-containing unnatural amino acids and subsequent bioorthogonal...

G-quadruplexes, one of the most significant secondary structure of nucleic acid, are formed by stacking G quartets, which received broad interests due to their involvement in telomere function, gene transcription and recombination. As for ligand, better selectivity for G-quadruplex against other DNA or RNA structures and higher ability to stabilize G-quadruplex are necessary. In addition, developing a new probe to recognize G-quadruplex is desired for utilizing G-quadruplex structure to relevant biological processes. In this study, we report a Cy5 labelled ligand (named PDP-Cy5) developed as a near-infrared fluorescent ligand for G-quadruplexes both in DNA and RNA. The results indicated that PDP-Cy5 selectively induced the formation of intramolecular G-quadruplexes with strong binding affinity. Furthermore, this Cy5 labelled ligand can effectively stabilize G-quadruplexes. Moreover, the direct visualization of G-quadruplexes in gel, even on cell level is realized by using PDP-Cy5.