Structurally well‐defined heterogeneous N‐glycoclusters are prepared on albumin via a double click procedure. The number of glycan molecules present, in addition to the spatial arrangement of glycans in the heterogeneous glycoclusters, plays an important role in the in vivo kinetics and organ‐selective accumulation through glycan pattern recognition mechanisms.

Abstract:We have developed a conceptually and methodologically novel self-assembled multilayer nickel nanoparticle (NP) catalyst -sulfur-modified gold-supported Ni NPs (SANi) -for organic synthesis. The SANi catalyst was easily prepared through a three-step procedure involving simultaneous in situ metal NP and nanospace organization. This unique method does not require any conventional preformed template for immobilizing and stabilizing NPs. SANi catalyzes carbon-carbon bond-forming cross-coupling, Kumada coupling, and Negishi coupling reactions under ligand-free conditions and can be used repeatedly for these reactions. Physical analysis of SANi showed that the active species in these reactions are self-assembled multilayer zerovalent Ni NPs with a size of~3 nm.

A one-pot three-component double-click process for preparing tumor-targeting agents for cancer radiotherapy is described here. By utilizing DOTA (or NOTA) containing tetrazines and the TCO-substituted aldehyde, the two click reactions, the tetrazine ligation (an inverse electron-demand Diels-Alder cycloaddition) and the RIKEN click (a rapid 6π-azaelectrocyclization), could simultaneously proceed under mild conditions to afford covalent attachment of the metal chelator DOTA or NOTA to biomolecules such as to albumin and anti-IGSF4 antibody without altering their activities. Subsequently, radiolabeling of DOTA- or NOTA-attached albumin and anti-IGSF4 antibody (an anti-tumor-targeting antibody) with [67Cu], a β−-emitting radionuclide, could be achieved in a highly efficient manner via a simple chelation with DOTA proving to be a more superior chelator than NOTA. Our work provides a new and operationally simple method for introducing the [67Cu] isotope even in large quantities to biomolecules, thereby representing an important process for preparations of clinically relevant tumor-targeting agents for radiotherapy.

A facile synthesis of an 211At-labeled immunoconjugate for α-emission therapy was achieved based on a one-pot three-component double click method.