[The Biological Activity of the Sevanol and Its Analogues].

Previously, from the plant Thymus armeniacus a new lignan sevanol was isolated, it's structure was elucidated and was shown that it effectively inhibits the acid-sensing channel ASIC3 and also exhibits a pronounced analgesic and anti-inflammatory effect. In this work biological activity of the sevanol analog obtained by chemical synthesis from simple precursors, the stereoisomer of sevanol and a precursor molecule represents a half of sevanol was measured in electrophysiological experiments on human ASIC3 channels expressed in Xenopus laevis oocytes. Measured inhibitory activity of a synthetic analogue coincided with the activity ofthe natural molecule. Stereoisomer showed inhibitory activity drop by about a third part, and the precursor molecule showed much less significant activity. In result the significance of functional groups and a spatial configuration of sevanol in order to biological activity was shown that is important to take into account for the optimal synthesis design as well as for new drugs development on its base.

Acid-sensing ion channels and their modulators.

According to a modern look acid-sensing ion channels (ASICs) are one of the most important receptors that perceive pH change in the body. ASICs represent proton-gated Na+-selective channels, which are expressed in neurons of the central and peripheral nervous system. These channels are attracting attention of researchers around the world, as they are involved in various physiological processes in the body. Drop of pH may occur in tissues in norm (e.g. the accumulation of lactic acid, the release of protons upon ATP hydrolysis) and pathology (inflammation, ischemic stroke, tissue damage and seizure). These processes are accompanied by unpleasant pain sensations, which may be short-lived or can lead to chronic inflammatory diseases. Modulators of ASIC channels activity are potential candidates for new effective analgesic and neuroprotection drugs. This review summarizes available information about structure, function, and physiological role of ASIC channels. In addition a description of all known ligands of these channels and their practical relevance is provided.

[Polypeptide toxin from sea anemone inhibiting proton-sensitive channel ASIC3].

Polypeptide toxin pi-AnmTX Hcr 1b-1 with a molecular weight 4537 Da was isolated from the whole body extract of sea anemone by a multistage liquid chromatography. The BLAST search algorithm revealed homology of the novel toxin amino acid sequence to the group of the known sea anemone toxins including BDS and APETx with similarity less then 50%. The toxin pi-AnmTX Hcr 1b-1 inhibited the amplitude of the fast component of integral ASIC3 current in electrophysiological studies on receptors expressed in Xenopus laevis oocytes. The calculated IC50 value was 5.5 +/- 1.0 microM. Among the known polypeptide toxins interacted with ASICs channels, the micro-AnmTX Hcr 1b-1 toxin is the least potent inhibitor that in our opinion correlates with a small amount of charged amino acid residues in its structure.

[Pseudomonas aeruginosa bacteriophage SN: 3D-reconstruction of the capsid and identification of surface proteins by electron microscopy].

The virulent P. aeruginosa bacteriophage SN belongs to the PB1-like species of the Myoviridae family. The comparatively small (66391 bp) DNA genome of this phage encodes 89 predicted open reading frames and the proteome involves more than 20 structural proteins. A 3D model of the phage capsid to approximately 18 A resolution reveals certain peculiarities of capsomer structure typical of only this bacteriophage species. In the present work recombinant structural proteins SN gp22 and gp29 were expressed and purified; and specific polyclonal antibodies were obtained. Immune-electron microscopy of purified phage SN using secondary gold-conjugated antibodies has revealed that gp29 forms a phage sheath, and gp22 decorates the capsid. Precise identification of multicopy major capsid proteins is essential for subsequent construction of gene-engineered phages bearing non-native peptides on their surfaces (phage display).