20.500.12556/RUL-185527 Načrtovanje, sinteza in vrednotenje zaviralcev bakterijskih transpeptidaz in metalobetalaktamaz raziskovalni podatki, obravnavani v doktorskem delu Design, synthesis and evaluation of bacterial transpeptidase and metallo-beta-lactamase inhibitors research data underlying the doctoral dissertation Odpornost po Gramu negativnih bakterij proti protimikrobnim učinkovinam predstavlja vse večjo grožnjo javnemu zdravju, razvoj novih učinkovin pa za širjenjem odpornosti zaostaja. Doktorsko delo raziskuje monobaktame, monociklične β-laktame, kot ogrodje za nove protibakterijske učinkovine in združuje dva komplementarna pristopa: razvoj monobaktamskih zaviralcev bakterijskih transpeptidaz s protibakterijskim delovanjem ter računalniško podprto odkrivanje zaviralcev metalo-β-laktamaz. Raziskovalni podatki, nastali v okviru dela, so organizirani v štiri metodološke sklope, ki si sledijo od načrtovanja spojin do njihovega biološkega vrednotenja. Prvi sklop obsega in silico podatke, pridobljene z metodami molekulskega modeliranja. Zajema izhodiščne in generirane knjižnice spojin s kemijskimi deskriptorji, podatki o dobavljivosti in biološki aktivnosti, ter podatke molekulskega sidranja, kjer so bile za izbrane tarčne encime, določene vezavne konformacije ligandov in ocenjene z ustreznimi cenilnimi funkcijami. Podatki so shranjeni v standardnih kemoinformacijskih formatih (.sdf, .csv, .pdb, .maegz) in delovnih tokovih programa KNIME. Drugi sklop predstavljajo podatki rentgenske kristalografije. Za izbrane komplekse encim-ligand, vključno s PBP1b* in NDM-1, so bili zbrani difrakcijski podatki na sinhrotronih ESRF in Diamond Light Source, obdelani v koordinatne modele in deponirani v podatkovno bazo Protein Data Bank s trajnimi identifikatorji. Ti podatki neposredno povezujejo računalniško načrtovanje z eksperimentalno potrjenim načinom vezave spojin. Tretji sklop obsega analitske podatke, potrebne za identifikacijo in karakterizacijo vseh sintetiziranih spojin. Vključuje spektre NMR (1H, 13C), podatke UPLC in LC-MS za določitev čistosti in identitete ter HRMS za potrditev točne mase spojin. Vsaka spojina je opremljena z interno oznako, ki jo preko priloženega šifranta povezuje s podatki v vseh treh analitskih sklopih. Četrti sklop zajema podatke biološkega vrednotenja, ločene na encimske teste in protibakterijsko testiranje. Encimski testi so bila izvedeni na izoliranih tarčnih encimih in vključujejo surove odčitke plošč ter izračunane vrednosti zaviralne aktivnosti. Protibakterijsko testiranje obsega določitev minimalnih inhibitornih koncentracij na izbranih bakterijskih sevih. 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. penicilin vezoči proteini metalo-β-laktamaze monociklični β-laktami sinteza konjugati protibiofilmske spojine strukturno podprto načrtovanje penicillin-binding proteins metallo-β-laktamaze monocyclic β-lactams synthesis conjugates antibiofilm compounds structure-based drug design true false false Slovenski jezik Angleški jezik Neznano 2026-08-07 10:24:57 2026-08-07 21:37:29 2026-08-08 04:08:09 0000-00-00 00:00:00 2026 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 2028-10-01 PREBERI_ME.docx PREBERI_ME.docx PREBERI ME 1 0AB9ACEA03C0DF188F17E336745B5799 8102f3e4dd8d549a60343ab9f3b90b8b918c7176bbc218aabf12877723e89b02 4ed031b6-924e-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=244137 sifrant.xlsx sifrant.xlsx Šifrant 1 D17A53F53FA2379D274E2AD5DF4850A5 e40f70bd2240443c7f39e7a6a957e535ecdea8db7fb558abfe8988fde11a47ee 751e3a07-9251-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=244148 1_In_silico_data.zip 1_In_silico_data.zip 1 In silico data 1 87C12ECDF86B10AA3DF47E38E02513FB 918efed06e035cc6d231f47e5f3d77e988051e39603a3e0e31b8dae821395198 4e8b0fb7-924e-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=244134 2_Rentgenska_kristalografija.zip 2_Rentgenska_kristalografija.zip 2 Rentgenska kristalografija 1 DB70E44CE688562E6DD81EE77FC46C15 e377c85cb2bf61849fd67a377fc16f6d1439f071c3bb642a1f101d833e130180 4ea018c3-924e-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=244135 HPS_NMR.zip HPS_NMR.zip HPS NMR 1 D086EE0674E9BAFAB772C643483FCABA 63eb79a02c893190eb09b2c6a31769bdd88a715a0a011da32b068c2d30089ee6 4f9d2599-924e-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=244145 Fakulteta za farmacijo Poskus: Laboratorij 0 0 0