Natan Koraj

Biography

Originally from a small village in the north of Croatia, I moved to a big city to study pharmacy at the Faculty of Pharmacy and Biochemistry, University of Zagreb. I discovered my love for science through bioanalytical method development at the faculty, which resulted in the Rector’s award and a publication. The next big challenge was my master’s thesis in the field of medicinal chemistry, where I developed potential novel antimalarials. My student researcher days concluded with exploration of glycobiology. After graduating, I explored working as a pharmacist and as a pharmaceutical representative before finally returning to my dear science.

Research project objectives

DC7 will perform virtual screening and hit analysis to identify FTs and STs inhibitors. Starting hits will be alternatively discovered by using DNA-encoded libraries screening of compounds vs FTs and STs by using DELopen technology to minimize the risk of hit identification failure. Hits will be synthesized and further optimized in terms of potency, target selectivity and cell permeability. Co-crystallization experiments of enzyme-inhibitor complexes will be performed to elucidate interactions X-ray crystallographic experiments or alternatively by NMR. These data will in turn allow structure-based design and new iterations towards lead compounds to be assayed in cell-based assays.

University of Ljubljana, Scientific field of Pharmacy

The host laboratories (Anderluh, UL FFA, Department of Pharmaceutical Chemistry) are equipped with modern equipment for molecular modelling (supermicro servers for high-performance computing equipped with modern scientific software packages – OpenEye, GOLD, MOE, BiosolveIT, KNIME, OpenBabel, Modeller, VMD/NAMD, GROMACS, BLAST, PyMol), and organic synthesis and nanomaterials, including 400-800MHz NMR spectroscopy facilities, state of the art LC/MS/MS systems), polarimeter, AutoChem system, microwave reactors, bench top reactor Parr 4560 HPLCs, flash purification systems (Biotage Isolera), FT-IR, and mass (GC/MS, ESI/MS) spectrometers, UV-Vis spectrophotometers, freeze dryers, and centrifuges. Furthermore, a dedicated laboratory is available for biochemical studies with several microplate readers (TECAN Safire II and BioTek Synergy H4, microplate sample processor (robotic pipetor) BioTek Precision XS), biolayer interferometry instrument (Sartorius Octet® R4 Protein Analysis System), ITC system for microcalorimetry (TA Instruments Nano), flow cytometers (Attune NxT flow cytometer with automated plate reader), gel and membrane imager (UVItec Alliance 9.7), centrifuges (Hereus Megafuge 16R, Thermo Scientific and StatSpin Cytofuge), ultracentrifuge (Thermo Scientific Sorvall WX), incubator (WTB BINDER). Full access to the literature databases (Reaxys, Web of Science, ScFinder) and on-line access to the primary literature.

Selected papers (10):

  1. Kokot M, Weiss M, Zdovc I, Senerovic L, Radakovic N, Anderluh M, Minovski N, Hrast M. Amide containing NBTI antibacterials with reduced hERG inhibition, retained antimicrobial activity against gram-positive bacteria and in vivo efficacy. Eur J Med Chem. 2023, 250, 115160. doi: 10.1016/j.ejmech.2023.115160.
  2. van Klaveren S, Dernovšek J, Jakopin Ž, Anderluh M, Leffler H, Nilsson UJ, Tomašič T. Design and synthesis of novel 3-triazolyl-1-thiogalactosides as galectin-1, -3 and -8 inhibitors. RSC Adv. 2022,12(29),18973-18984. doi: 10.1039/d2ra03163a.
  3. Girardi B, Manna M, Van Klaveren S, Tomašič T, Jakopin Ž, Leffler H, Nilsson UJ, Ricklin D, Mravljak J, Schwardt O, Anderluh M. Selective Monovalent Galectin-8 Ligands Based on 3-Lactoylgalactoside. ChemMedChem. 2022,17(3):e202100514. doi: 10.1002/cmdc.202100514.
  4. Hassan M, Baussière F, Guzelj S, Sundin AP, Håkansson M, Kovačič R, Leffler H, Tomašič T, Anderluh M, Jakopin Ž, Nilsson UJ. Structure-Guided Design of d-Galactal Derivatives with High Affinity and Selectivity for the Galectin-8 N-Terminal Domain. ACS Med Chem Lett. 2021, 12(11),1745-1752. doi: 10.1021/acsmedchemlett.1c00371.
  5. Anderluh, M.; Berti, F.; Bzducha‐Wróbel, A.; Chiodo, F.; Colombo, C.; Compostella, F.; Durlik, K.; Ferhati, X.; Holmdahl, R.; Jovanovic, D.; Kaca, W.; Lay, L.; Marinovic‐Cincovic, M.; Marradi, M.; Ozil, M.; Polito, L.; Reina, J.J.; Reis, C.A.; Sackstein, R.; Silipo, A.; Švajger, U.; Vaněk, O.; Yamamoto, F.; Richichi, B.; S. J. van Vliet, Recent advances on smart glycoconjugate vaccines in infections and cancer. FEBS J., 2021, doi: 10.1111/febs.15909
  6. Kokot M, Weiss M, Zdovc I, Hrast M, Anderluh M, Minovski N. Structurally Optimized Potent Dual-Targeting NBTI Antibacterials with an Enhanced Bifurcated Halogen-Bonding Propensity. ACS Med Chem Lett. 2021, 12(9), 1478-1485. doi: 10.1021/acsmedchemlett.1c00345.
  7. Hassan M, van Klaveren S, Håkansson M, Diehl C, Kovačič R, Baussière F, Sundin AP, Dernovšek J, Walse B, Zetterberg F, Leffler H, Anderluh M, Tomašič T, Jakopin Ž, Nilsson UJ. Benzimidazole-galactosides bind selectively to the Galectin-8 N-Terminal domain: Structure-based design and optimisation. Eur J Med Chem. 2021, 223, 113664. doi: 10.1016/j.ejmech.2021.113664.
  8. Weiss M, Loi EM, Sterle M, Balsollier C, Tomašič T, Pieters RJ, Gobec M, Anderluh M. New Quinolinone O-GlcNAc Transferase Inhibitors Based on Fragment Growth. Front Chem. 2021, 9., 666122. doi: 10.3389/fchem.2021.666122.
  9. Anderluh M, Berti F, Bzducha-Wróbel A, Chiodo F, Colombo C, Compostella F, Durlik K, Ferhati X, Holmdahl R, Jovanovic D, Kaca W, Lay L, Marinovic-Cincovic M, Marradi M, Ozil M, Polito L, Reina-Martin JJ, Reis CA, Sackstein R, Silipo A, Švajger U, Vaněk O, Yamamoto F, Richichi B, van Vliet SJ. Emerging glyco-based strategies to steer immune responses. FEBS J. 2021, 288(16), 4746-4772. doi: 10.1111/febs.15830.
  10. Kolarič A, Germe T, Hrast M, Stevenson CEM, Lawson DM, Burton NP, Vörös J, Maxwell A, Minovski N, Anderluh M. Potent DNA gyrase inhibitors bind asymmetrically to their target using symmetrical bifurcated halogen bonds. Nat Commun. 2021, 12(1), 150. doi: 10.1038/s41467-020-20405-8.