1.

Populations of the three major backbone conformations in 19 amino acid dipeptides

Dipeptides are amino acids blocked with an acetyl and an N-methyl group. The amino acids in dipeptides have structural properties similar to amino acid residues in proteins; this is why structures of dipeptides are important for understanding structures of proteins. We have determined the dipeptide structures of 19 basic amino acids in a water solution. Using spectroscopic methods, we have demonstrated the presence of three conformations of dipeptides in water: the PII, ß, and the ?R. The proportion of the ?R conformation in all dipeptides is surprisingly low (( 10%).

COBISS.SI-ID: 4611098

2.

Interactions at the bilayer interface and receptor site induced by the novel synthetic pyrrolidinone analog MMK3

A new type of AT1 antagonists have been designed and synthesized, which have significant antihypertensive activity. We used a combination of experimental (NMR, Raman, DSC, small angle X-ray scattering) and theoretical methods (MD) for precise determination of ligand-membrane and ligand-receptor interactions, which is required for the design of analogues with improved biological profile. We have shown that activity of new antagonists can be improved in two ways: through the thermodynamic effects on the lipid bilayers and through the stereoelectronic active site requirements.

COBISS.SI-ID: 4385050

3.

Determination of binding site of novel rhodanine MurD inhibitors

By application of NMR methods we have shown that novel rhodanine MurD inhibitors interact with binding site of UDP substrate and are located in the uracil-binding pocket. The possibility of binding to UDP and ATP binding sites have been proposed, which is based on the molecular structure of rhodanine derivatives and studies of tridimensional structure of UDP and ATP binding sites. Comparison studies of chemical shift perturbations of MurD methyl groups upon binding of known inhibitors, UDP substrate, and AMPPCP have excluded the binding of novel inhibitors to ATP binding site.

COBISS.SI-ID: 2743921

4.

Hyperbranched poly(esteramides) as solubility enhancers for poorly water-soluble drug glimepiride.

We studied interactions between the antidiabetic drug glimepiride and hyperbranched polymer with large number of functional groups. We applied this type of polymers as solubility enhancer and as drug carrier. The results of IR measurements revealed that improved solubility results from a complex formed by glimepiride and hyperbranched polymer. The complex glimepiride stays in amorphous form up to 5% (w/w). Above this limit, glimepiride crystallizes as a separate phase. The existence of molecules of glimepiride in amorphous phase is the reason for the increase of solubility.

COBISS.SI-ID: 2834289

5.

Inhibition of human sterol delta 7-reductase and other post-lanosterol enzymesby a novel inhibitor of cholesterol synthesis.

The screening of the novel cholesterol-lowering agents, 1-phenethyl-4-(2-(pyridinyl)ethyl)piperazine derivatives, was performed by 3H metabolic labelling of HepG2 cells, extraction of radiolabeled sterols, and reverse phase HPLC separation. 2-(4-phenethylpiperazin-1-yl)-1-(pyridine-3-yl)ethanol was characterized further and analyzed by GC-MS allowing simultaneous separation and quantification of nine late cholesterol intermediates. Experiments supported by the mathematical model of the flux of sterol intermediates indicated that human DHCR7 is the major target.

COBISS.SI-ID: 27512281