Bioorthogonal click-to-release reaction for regulating iodo-BODIPY PDT probe / 药学学报

In this study, we synthesized six tetrazine-dipyrromethene boron difluoride (BODIPY) probes and achieved a remarkable up to 14-fold increase in singlet oxygen yield via tetrazine bioorthogonal click-to-release reactions. We systematically investigated the photodynamic activity of these probes, revealing crucial structure-activity relationships. Additionally, we evaluated the stability and release kinetics of these probes and identified P5 and P6 as ideal candidates for photodynamic therapy in live cells. This innovative strategy opens new avenues for fine-tuning the photodynamic properties of BODIPY dyes, thereby expanding their utility in cancer therapy.

Design and synthesis of tetrazine bioorthogonal fluorogenic probes / 药学学报

Bioorthogonal fluorogenic probes are becoming an ideal tool for live-cell fluorescence imaging. With the tetrazine bioorthogonal fluorogenic probe that displays fluorescence enhancement, the tetrazine plays the dual-role of a bioorthogonal reaction unit and the fluorescence quenching unit. The "off" and "on" states of the fluorescence probe are mainly controlled through inverse electron demand Diels-Alder (IEDDA) bioorthogonal reaction. We designed a series of turn-on tetrazine fluorescent probes with Donor-π-Acceptor (D-π-A) structure to achieve a high signal-to-noise ratio and specificity of fluorescence imaging. This series of probes reacted with the dienophile bicyclononyne, and then generated pyridazine structure in-situ that acted as an electron acceptor, resulting in a new D-π-A effect of fluorescent dyes, turning on the intramolecular charge transfer (ICT) effect. By adjusting the electron-donating groups and the degree of conjugation, tunable fluorescence spectra between 400-647 nm with fluorescence turn-on enhanced up to 500-fold have been achieved. This research lays the foundation for the further optimization of tetrazine bioorthogonal fluorescent probes and their applications in molecular imaging and biomedical fields.

Tetrazine bioorthogonal click-to-release reaction for releasing peptides / 药学学报

This paper aimed to investigate the release efficiency of peptide at carbon terminal triggered by tetrazine bioorthogonal click-to-release reaction, and further explored the potential application of this reaction in functional modification and mild cleavage in solid-phase peptide synthesis. Thirteen peptide derivatives modified by trans-cyclooctene (TCO) were designed and synthesized, which were reacted with tetrazine to release the peptides. The results showed that the release rates of peptide were 90.0% to 97.7% in one hour. The strategy has good compatibility with the functional side-groups and the length of peptides, which expands the applications scope of tetrazine bioorthogonal click-to-release reaction. At the same time, a novel bifunctional trans-cyclooctene molecule was designed and synthesized. The active peptide GIRLRG was modified by fluorophore on the solid-phase resin, and released through tetrazine click-to-release reaction under mild condition, providing a new strategy for the solid-phase modification and release strategy of the peptide.