We have developed a pH-responsive phosphoramidate-based linker scaffold designed to release cargo in the endosomal/lysosomal compartments in target cells. The tunability of the phosphoramidate linker enables broad applicability as pH-responsive controlled release platform. The acid-responsive linker contains two key structural components, a biologically stable and cleavable phosphoramidate scaffold and a self-immolative spacer. The payload is cleanly released when the self-immolative spacer undergoes hydrolysis from the phosphoramidate scaffold through exposure to acidic conditions. This linker is also click-ready and water soluble to again in bioconjugation to an array of relevant therapeutic agents. These acid-responsive linkers are only receptive to pH and do not require intracellular enzymatic action to initiate release. We optimized the phosphoramidate linker for controlled-release of both amine- and alcohol- based payloads. Herein, we will demonstrate applications of these acid-responsive phosphoramidate scaffolds for the controlled release of payloads such as fluorescent dyes or chemotherapeutic drugs.

Modular phosphoramidate-based pH-responsive linkers for controlled release

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.