Resistance of Gram-negative bacteria to antimicrobial agents represents a growing threat to public health, and the development of new antimicrobial agents continues to lag behind the spread of resistance. This doctoral work investigates monobactams, monocyclic β-lactams, as a scaffold for novel antibacterial agents and combines two complementary approaches: the development of monobactam-based bacterial transpeptidase inhibitors with antibacterial activity, and computer-aided discovery of metallo-β-lactamase inhibitors. The research data generated within this work are organized into four methodological sections, following the workflow from compound design to biological evaluation.
The first section comprises in silico data obtained through molecular modeling methods. It includes starting and generated compound libraries with chemical descriptors, availability data and biological activity data, as well as molecular docking data, where binding conformations of ligands were determined for selected target enzymes and scored using appropriate scoring functions. Data are stored in standard cheminformatics formats (.sdf, .csv, .pdb, .maegz) and KNIME workflow files.
The second section consists of X-ray crystallography data. For selected enzyme-ligand complexes, including PBP1b* and NDM-1, diffraction data were collected at the ESRF and Diamond Light Source synchrotrons, processed into coordinate models, and deposited in the Protein Data Bank with permanent identifiers.
The third section comprises analytical data required for the identification and characterization of all synthesized compounds. It includes NMR spectra (1H, 13C), UPLC and LC-MS data for purity and identity determination, and HRMS data for confirmation of exact mass. Each compound is assigned an internal code that, through the attached compound key, links it to data across all three analytical sections.
The fourth section covers biological evaluation data, divided into enzyme assays and antibacterial testing. Enzyme assays were performed on isolated target enzymes and include raw plate readings and calculated inhibitory activity values. Antibacterial testing includes determination of minimum inhibitory concentrations against selected bacterial strains.
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