Modulating Local Charge Distribution of Carbon Nitride for Promoting Exciton Dissociation and Charge-Induced Reactions.

The sustainable light can generate reduction and oxidation centers in situ through the generation of photoexcited electrons and holes in the presence of photocatalyst. However, the photoexcited electrons and holes have huge Coulombic attraction and high exciton binding energy due to the weak screening effect and dielectric properties in many low-dimensional conjugated polymers, such as carbon nitride. Reducing the exciton binding energy of carbon nitride and promoting the conversion of excitons into free charge carriers are necessary for improving the activity of photocatalytic reactions but still very challenging. Here, by introducing amino-cyano functional groups into carbon nitride, it is demonstrated that excitons can be effectively dissociated into electrons and holes by finely controlling the charge distribution of heptazine ring. It is found that carbon nitride with heptazine rings of positive charge distribution can greatly reduce the exciton binding energy to 24 from 71 meV. Compared with heptazine ring having negative charge distribution, heptazine ring with positive charge distribution can increase photocatalytic hydrogen production of carbon nitride by up to ten times. This work provides an easy way to promote the dissociation of excitons in carbon nitride by regulating the charge distribution.

Development of Integrin Targeting Chimeras (ITACs) for the Lysosomal Degradation of Extracellular Proteins.

The emerging of lysosomal targeting chimera (LYTAC) expands the field of targeted protein degradation (TPD) to include the extracellular proteins for precise depletion. However, most of the reported LYTACs either induce ubiquitous degradation of the protein of interest (POI) in a broad range of tissues or specifically target liver cells. More tissue-selective degraders are highly desirable. Herein, we describe the development of cyclic RGD (cRGD) peptide-antibody conjugates as a novel class of integrin targeting chimeras (ITACs) with potential cancer selectivity. Our results indicate that the ITACs are able to recruit integrin to induce the degradation of both soluble and membrane targets in the lysosome. We observed higher efficiency of ITACs on degrading membrane protein in cancer cells, providing a promising platform for cancer-selective TPD strategy.

Development of Oligomeric Mannose-6-phosphonate Conjugates for Targeted Protein Degradation.

Lysosome targeting chimeras (LYTACs) are a new protein degradation strategy that has recently emerged. LYTACs utilize the native cell internalization process in the body to target and degrade therapeutically relevant extracellular proteins via the lysosomal pathways. The first lysosomal internalization receptor recently used for LYTACs is the mannose-6-phosphate receptor (M6PR). M6PR is expressed across most cell types, making it ideal for internalization and degradation of numerous extracellular proteins. Herein, we report the development of a series of structurally well-defined mannose-6-phosphonate (M6Pn)-peptide conjugates that are capable of linking to a variety of targeting ligands for proteins of interest and successfully internalizing and degrading those proteins through M6PR. This will greatly facilitate the development of M6Pn based LYTACs for therapeutic applications.