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We introduce an enzyme mechanism-based method (EMBM) aimed at rational design of chemical sites (CS) of reaction coordinate analog inhibitors. The energy of valence reorganization of CS, caused by the formation of the enzyme-inhibitor covalent complex, is accounted for by new covalent descriptors W1 and W2. We considered CS fragments with a carbonyl… (More)
Various mechanisms for the reversible formation of a covalent tetrahedral complex (TC) between papain and peptidyl aldehyde inhibitors were simulated by DFT calculations, applying the quantum mechanical/self consistent reaction field (virtual solvent) [QM/SCRF(VS)] approach. Only one mechanism correlates with the experimental kinetic data. The His-Cys… (More)
We report about the preparation of novel protected Nα(ω-drug) amino acid building units and their straightforward incorporation in solid phase synthesis for the preparation of peptide-drug conjugates. These building units were synthesized applying various coupling methods between anticancer drugs and the side chains of different Nα protected amino acids.… (More)
Project Title of the project: 'Quantum chemical (QM) and quantum mechanics / molecular mechanics (QM/MM) studies of catalytic mechanism and inhibition of cysteine proteases'
Purification of proteins on a large scale is a complex multistep process, and alternative economic strategies are required. This study presents a novel approach (Affinity Sinking, AS) for purification of native proteins utilizing nonimmobilized modified ligands. The nonimmobilized state of the ligand circumvents the need for immobilizing ligands to… (More)
We synthesized new broad spectrum antibacterial cationic peptidomimetics centered on a hydrophobic 1,4-dihydropyridine (1,4-DHP) scaffold. The synthesis involves the preparation of the scaffold in a three step Hantzsch reaction followed by simultaneous coupling of the 1,4-DHP scaffold to two dipeptides bearing cationic side chains. The synthesized… (More)