Ligand-Directed N-Sulfonyl Pyridone Chemistry for Selective Native Protein Labeling and Imaging in Live Cell.

Advances in biocompatible organic chemistry applicable for endogenous protein modification under live-cell conditions have been longed as these can produce an important tool for the elucidation of a variety of biological phenomena. However, there are still various obstacles to be overcome, such as the limited repertories of the reaction modes, the slow reaction kinetics, and the insufficient specificity for endogenous protein modification. We have recently reported a new type of affinity-based labeling technique termed ligand-directed (LD) chemistry that does not need any genetic manipulation, which shows a sharp contrast with other strategies including peptide/enzyme-tag methods or bioorthogonal chemistry-based methods.

Graftable SCoMPIs enable the labeling and X-ray fluorescence imaging of proteins.

Bio-imaging techniques alternative to fluorescence microscopy are gaining increasing interest as complementary tools to visualize and analyze biological systems. Among them, X-ray fluorescence microspectroscopy provides information on the local content and distribution of heavy elements ( ≥ 14) in cells or biological samples. In this context, similar tools to those developed for fluorescence microscopy are desired, including chemical probes or tags.

Live-Cell Protein Sulfonylation Based on Proximity-driven N-Sulfonyl Pyridone Chemistry.

The development of bioorthogonal approaches for labeling of endogenous proteins under the multimolecular crowding conditions of live cells is highly desirable for the analysis and engineering of proteins without using genetic manipulation. N-Sulfonyl pyridone (SP) is reported as a new reactive group for protein sulfonylation. The ligand-directed SP chemistry was able to modify not only purified proteins in vitro, but also endogenous ones on the surface of and inside live cells selectively and rapidly, which allowed to convert endogenous proteins to FRET-based biosensors in situ.

Anti-MUC1 Aptamer/Negatively Charged Amino Acid Dendrimer Conjugates for Targeted Delivery to Human Lung Adenocarcinoma A549 Cells.

We previously developed a negatively charged amino acid dendrimer to address the safety concerns associated with the constituent unit of these systems, which resulted in the formation of a sixth-generation glutamic acid-modified dendritic poly(L-lysine) system (KG6E). The aim of this study was to develop a nanocarrier for targeted drug delivery into cancer cells. In this study, we have synthesized a conjugate material consisting of anti-mucin 1 (MUC1) aptamer (anti-MUC1 apt) and KG6E (anti-MUC1 apt/KG6E) for targeted drug delivery to human lung adenocarcinoma A549 cells, which express high levels of the MUC1.