In the framework of the doctoral dissertation, Jure Borišek designed and experimentally evaluated the inhibitors of cathepsin K (Cat K) and autolysin E (AtlE). In the first part of his work Jure designed a new series of Cat K inhibitors based on N-(functionalized benzoyl) homocycloleucylglycinonitrile scaffold using in silico approach. Synthesized compounds were highly selective for Cat K when compared with cathepsins L and S with the Ki values in the 10-30 nanomolar range. The kinetic studies revealed that the new compounds exhibited reversible tight binding to Cat K, while the X-ray structural studies showed covalent and noncovalent binding between the nitrile group and the catalytic cysteine Cys25 site. The second part of his research was dedicated to development of novel potential AtlE inhibitors of bacterial strain Staphylococcus aureus (S. aureus). Using computer-aided structural drug design methods and pharmacophore modeling, he managed to discover a novel chemical class representing potential AtlE inhibitors, which had binding affinities in the low micromolar range.
D.09 Tutoring for postgraduate students
COBISS.SI-ID: 282440704Guest editors of a special issue of SAR and QSAR in environmental research (Print), Vol. 29, iss. 8 (2018) - dedicated to the 18th International Conference on QSAR in Environmental and Health Sciences (QSAR 2018), June 11-15, Bled, Slovenia
C.03 Guest-associated editor
COBISS.SI-ID: 6451994During the invited lecture, the method for optimization of counter-propagation artificial neural networks with cross-validation and genetic algorithm was presented. It was shown how counter-propagation neural network models can be used for read-across using software developed in our laboratory. The lecture was given during international conference “Central European School on Physical Organic Chemistry” with the conference general subject “From Calculation to Experiment in Chemistry and Biology”. The presented subject is important for researchers in the field of organic and physical chemistry that are designing new organic compounds.
B.04 Guest lecture
COBISS.SI-ID: 39552517Here we report on in silico approaches, including structure based molecular modelling and Quantitative Structure Activity Relationship (QSAR) modelling towards inhibition of peptidoglycan metabolising enzymes. Based on substrate molecules similarity between peptidoglycan synthesizing and peptidoglycan degrading enzymes we anticipate similar ligand binding patterns and in some segments also similar ligands/inhibitors. Commercial and freely available software tools were applied for structural comparison of peptidoglycan metabolising enzymes’ binding sites. Based on published inhibitors of peptidoglycan synthesizing enzymes we also developed QSAR models for muramyl ligase inhibitors prediction. These models will be, at appropriate structural similarity rate of ligands or binding sites of enzymes, that synthesize and enzymes that degrade peptidoglycan, suitable for initial scanning of potential inhibitors of autolysines, which are not yet investigated nor discovered. Consequently, this study could significantly contribute to structure based design of antibacterial agents of novel drug target.
B.04 Guest lecture
COBISS.SI-ID: 6235418Abstract: The present invention relates to novel monocyclic fragments coupled to aminopiperidine naphthyridine moiety comprising antibacterial activity. These compounds can be used for treating bacterial infections, including those that nowadays are difficult and almost impossible to treat with the existing antibacterial agents. Description: This invention relates to novel antibacterial compounds grounded on innovative monocyclic fragments coupled to aminopiperidine naphthyridine scaffold, which can be used in treating bacterial infections. Herein disclosed novel antibacterial compounds can also be capable of treating bacterial infections caused by resistant bacterial strains, which nowadays are difficult to treat with the existing antibacterial chemotherapy.
F.32 International patent
COBISS.SI-ID: 6571802