Because chemotherapy is still dependent on highly toxic compounds that lack selectivity, their side effects reduce patient quality of life and often result in complications that lead to patient death. The Boyce lab develops protease-cleavable linkers to turn chemotherapeutics into highly selective prodrugs that would overcome these challenges by enabling drug activation in the tumor microenvironment. These linkers are also used to develop improved antibody-drug conjugates (ADCs) that minimize neutropenia, a common side effect for all FDA-approved protease-cleavable ADCs due to premature drug release. Furthermore, we design biomolecular prodrugs to combat cancer resistance and develop new prodrug therapies for infectious diseases.