Bacterial infections are a growing global health threat, worsened by the rise of antibiotic resistance, particularly to β-lactam antibiotics. These antibiotics target penicillin-binding proteins (PBPs) to disrupt bacterial cell wall synthesis, but the emergence of β-lactamase (BL)-producing strains has rendered them ineffective. The spread of these resistance mechanisms within bacterial populations contributes significantly to the current antibiotic crisis. Moreover, existing treatments often disrupt the host's gut microbiota, complicating efforts to manage resistance. We have recently developed a prodrug, AcephPT, designed to selectively target and inhibit BL-producing bacteria while sparing non-resistant strains. AcephPT preferentially reacts with BLs over PBPs, but in vitro studies show reduced hydrolysis rates compared to other β-lactam substrates. To overcome this limitation, we aim to develop next generation prodrugs that maintain biased recognition with both serine and metallo-BLs while increasing the hydrolytic rate. A modular synthetic approach has been used to optimize desirable properties and test metal-dependent activity of individual fragments before generating entire prodrugs. To screen molecules, we validate activation of β-lactam hydrolysis by using NMR spectroscopy and determine biased activity in microculture bacterial growth. Herein, we present a library of compounds as both fragments and conjugated prodrugs to validate the fragment-based drug design for development of our next generation β-lactam prodrug.