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'
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)
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)