Designing cell-targeted therapeutic proteins reveals the interplay between domain connectivity and cell binding.

ABSTRACT: The therapeutic efficacy of cytokines is often hampered by severe side effects due to their undesired binding to healthy cells. One strategy for overcoming this obstacle is to tether cytokines to antibodies or antibody fragments for targeted cell delivery. However, how to modulate the geometric configuration and relative binding affinity of the two domains for optimal activity remains an outstanding question. As a result, many antibody-cytokine complexes do not achieve the desired level of cell-targeted binding and activity. Here, we address these design issues by developing a computational model to simulate the dynamics and binding kinetics of natural and engineered fusion proteins such as antibody-cytokine complexes. To verify the model, we developed a modular system in which an antibody

SUBMITTER: Robinson-Mosher A 

PROVIDER: S-EPMC4241446 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature