The catalytic properties of organophosphate hydrolase (OPH) containing a hexahistidine tag His6 (His6-OPH) and purified to 98% homogeneity were investigated. The pH optimum of enzymatic activity and isoelectric point of His6-OPH, which were shown to be 10.5 and 8.5, respectively, are shifted to the alkaline range as compared to the same parameters of the native OPH. The recombinant enzyme possessed improved catalytic activity towards S-containing substrates: the catalytic efficiency of methylparathion hydrolysis by His6-OPH is 4.2 x 10(6) M(-1) x sec(-1), whereas by native OPH it is 3.5 x 10(5) M(-1) x sec(-1).

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Rabies virus is a prototypical neurotropic virus that causes one of the most dangerous zoonotic diseases in humans. Humanized or fully human monoclonal antibodies (mAb) that neutralize rabies virus would be the basis for powerful post-exposure prophylaxis of rabies in humans, having several significant benefits in comparison with human or equine rabies polyclonal immunoglobulins. The most advanced antibodies should broadly neutralize natural rabies virus isolates, bind with conserved antigenic determinants of the rabies virus glycoprotein, and show high neutralizing potency in assays in vivo. The antibodies should recognize nonoverlapping epitopes if they are used in combination. This review focuses on basic requirements for anti-rabies therapeutic antibodies. The urgency in the search for novel rabies post-exposure prophylaxis and methods of development of anti-rabies human mAb cocktail are discussed. The rabies virus structure and pathways of its penetration into the nervous system are also briefly described.

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The main aim of our work was to create a full-length bispecific antibody (BsAb) as a vehicle for the targeted delivery of interferon-beta (IFN-β) to ErbB2+ tumor cells in the form of non-covalent complex of BsAb and IFN-β. Such a construct is a CrossMab-type BsAb, consisting of an ErbB2-recognizing trastuzumab moiety, a part of chimeric antibody to IFN-β, and human IgG1 Fc domain carrying knob-into-hole amino acid substitutions necessary for the proper assembly of bispecific molecules. The IFN-β- recognizing arm of BsAb not only forms a complex with the cytokine but neutralizes its activity, thus providing a mechanism to avoid the side effects of the systemic action of IFN-β by blocking IFN-β Interaction with cell receptors in the process of cytokine delivery to tumor sites. Enzyme sandwich immunoassay confirmed the ability of BsAb to bind to human IFN-β comparable to that of the parental chimeric mAb. The BsAb binds to the recombinant ErbB2 receptor, as well as to lysates of ErbB2+ tumor cell lines. The inhibition of the antiproliferative effect of IFN-β by BsAb (IC50 = 49,3 µg/mL) was demonstrated on the HT29 cell line. It can be proposed that the BsAb obtained can serve as a component of the immunocytokine complex for the delivery of IFN-β to ErbB2-associated tumor cells.

New trends in chemistry induced by genetic engineering and genomic information are analyzed. Genomic information and bioinformatics make the identification of all molecular participants of biological processes possible. The methods of identification of enzymeactive sites from sequence data were demonstrated. The problems of "chemical proteomics" were formulated and analyzed. New biocatalytic processes based on a new generation of enzymes, including CO 2 reduction and enzyme fuel cell construction, are demonstrated. It was shown that in many reactions the enzymes are substantially more efficient in comparison with classical chemical catalysts. The creation of recombinant proteins from unnatural amino acids is demonstrated, and organisms containing such proteins are described. The new trends of proteomics and bioanalytical chemistry in the postgenomic era are discussed.

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