Probing cellular uptake using heterobivalent constructs

Several conjugation techniques are central to improving intracellular delivery of bioactive small molecules and their constructs. However, it remains poorly understood whether and how they may modify the overall biological outcome. We addressed this issue by having developed a focused library of heterobivalent constructs based on Rho and myosin light chain kinase inhibitors to probe various possible scenarios. By comparing induction of a phenotype of interest vs. cell viability vs. cellular uptake, we demonstrate that such conjugates indeed lead to divergent cellular outcomes.