Molecular dynamics study of the Cu2+ binding-induced "structuring" of the N-terminal domain of human prion protein.

In this work, we report molecular dynamics simulations on a fragment of the human prion protein spanning residues 31-120, with copper(II) bound to the repeat region in several ways corresponding to the known intra- and inter-repeat coordination modes, or to the metal site located at His111. The results of this study point to a different structuring tendency of the protein fragment depending on copper binding mode, with the highest degree of structuring in the case of intrarepeat Cu(II) coordination corresponding to high copper concentration.

Synthesis, immunological activity and computational study of 5-amino-3-methyl-4-isoxazolecarboxylic acid semicarbazides and thiosemicarbazides.

A series of 5-amino-3-methyl-4-isoxazolecarboxylic acid semicarbazides and thiosemicarbazides (M1-M9) were obtained by reacting 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide with isocyanate and isothiocyanate. In order to determine structure-activity relationships for the series of nine compounds (M1-M9) geometry optimization was carried out using quantum-chemical DFT calculations at B3LYP/6-31g* level. The compounds, administered to mice at 1 microg or 10 microg doses, four hours prior to immunization with sheep erythrocytes (SRBC), significantly suppressed the primary, humoral immune response in mice as measured by the number of antibody-forming cells (AFC) in the spleens. Structure/activity relationships, regarding the studied compounds, were discussed.