A molecular dynamics study of protein denaturation induced by sulfonate-based surfactants.

Microsecond timescale explicit-solvent atomistic simulations were carried out to investigate how anionic surfactants modulate protein structure and dynamics. We found that lysozyme undergoes near-complete denaturation at the high concentration (> 0.1 M) of sodium pentadecyl sulfonate (SPDS), while only partial denaturation occurs at the concentration slightly below 0.1 M. In large part, protein denaturation is structurally manifested by disappearance of helical segments and loss of tertiary interactions. The computational prediction of the extent of burial of cysteine residues was experimentally validated by measuring the accessibility of the respective sulfhydryl groups. Overall, our work indicates an interesting synergy between electrostatic and hydrophobic contributions to lysozyme's denaturation process by anionic surfactants. In fact, first disulfide bridges and hydrogen bonds from protein surface to SPDS head groups loosen the protein globule followed by fuller denaturation via insertion of the surfactant's hydrophobic tails into the protein core.

Anti-tumor effect investigation of obtustatin and crude Macrovipera lebetina obtusa venom in S-180 sarcoma bearing mice.

Over the last few decades, research on snake venom toxins has provided not only new tools to decipher molecular details of various physiological processes, but also inspiration to design and develop a number of therapeutic agents. Isolated from the venom of Macrovipera lebetina obutusa (MLO), obtustatin represents the shortest known snake venom monomeric disintegrin specific inhibitor of α1ß1 integrin. This low molecular weight peptide revealed a potent therapeutic effect on melanoma progression. Its oncostatic effect was related to the inhibition of angiogenesis. The aim of the proposed investigation was to study the influence of obtustatin and crude MLO venom on the S-180 sarcoma growth in vitro and in vivo. A S-180 sarcoma bearing mouse model, histological examination, DNA retardation assay were utilized to investigate the anti-tumor effects of MLO and obtustatin. In addition, some biochemical tests (chemiluminescence-ChL, TBA-test) were applied to elucidate the influence of obtustatin and crude MLO venom on the S-180 sarcoma. The size of tumor was significantly inhibited by MLO venom and obtustatin with the inhibitory rate of 50% and 33% at the doses of 10 µg/mouse and 1mg/kg/day respectively. Both ChL and MDA decrease in the two treated groups. Both obtustatin and MLO venom have an anticancer activity and might be candidates for the treatment of malignant sarcoma. All our results have shown that both obtustatin and MLO venom have an anticancer activity and might be candidates for the treatment of malignant sarcoma.