In vitro effect of Knotolan, a new lignan from Abies sibirica, on the growth of hormone-dependent breast cancer cells.

Here we present antiestrogenic effects of Knotolan, a new dietary lignan from Abies sibirica raw material. Knotolan abolished growth-stimulating effects of 17ß-estradiol on hormone-dependent MCF-7 cells.

[Synthesis, NMR and conformational studies of fucoidan fragments. VI. Fragments, content of alpha-(1--->2)-bound fucobioside unit]. / Sintez, IaMR i konformatsionnye issledovaniia fragmentov fukoidanov. VI. Fragmenty, soderzhanie alpha-(1--->2)-sviazannoe fukobiozidnoe zveno.

A series of selectively sulfated di- and trisaccharide derivatives corresponding to the potential fragments of fucoidans with a (1-->2)-alpha-bound fucobioside unit were synthesized and studied by 1H and 13C NMR spectroscopy. NOE experiments and molecular modeling were used for a conformational analysis of the compounds synthesized. In the case of disaccharides, the experimental NOE values were found to agree with those obtained using modeling with the use of density functional theory (DFT) and differ from those resulting from modeling by the molecular mechanics MM3 force field. Trisaccharide fragments partially or completely sulfated in position 4 turned out to be correctly described by both MM3 force field and DFT computation. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 2; see also http://www.maik.ru.

[Neoglycoconjugates based on dendrimeric poly(aminoamides)]. / Neoglikokon''iugaty na osnove dendrimernykh poli(aminoamidov).

Neoglycoconjugates containing 4, 8, 16, 32, and 64 terminal residues of B-disaccharide (BDI) or N-acetylneuraminic acid (Neu5Ac) attached to poly(aminoamide)-type dendrimers (PAMAMs) were synthesized. The ability of BDI conjugates to bind natural xenoantibodies (anti-BDI antibodies) and the ability of Neu5Ac conjugates to inhibit the hemagglutinin-mediated adhesion of influenza virus were studied. The biological activity of PAMAM conjugates turned out to be higher than that of free carbohydrate ligands, but less than that of multivalent glycoconjugates based on other types of synthetic polymeric carriers. A conformational analysis of PAMAM matrices and resulting conjugates was performed to determine the statistical distances between carbohydrate ligands. The computations revealed the tendency of the PAMAM chains toward compaction and formation of dense globules. The process results in a decrease in the distances between the carbohydrate ligands in the conjugates and, hence, could affect the ability of glycoconjugates to efficiently bind the polyvalent carbohydrate-recognizing proteins. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no. 6; see also http://www.maik.ru.

Xenotransplantation: in vitro analysis of synthetic alpha-galactosyl inhibitors of human anti-Galalpha1-->3Gal IgM and IgG antibodies.

Pig-to-human xenotransplantation might be an option to overcome the increasing shortage of human donor organs. However, naturally occurring antibodies in human blood against the Galalpha1-->3Gal antigen on pig endothelial cells lead to hyperacute or, if prevented, acute or delayed vascular rejection of the pig graft. The purpose of this study was therefore to evaluate synthetic oligosaccharides with terminal Galalpha1-->3Gal to inhibit antigen-binding and cytotoxicity of anti-alphaGal antibodies against pig cells. Different oligosaccharides were synthesized chemically and by a combined chemico-enzymatic approach. These included monomeric di-, tri-, and pentasaccharides, a polyacrylamide-conjugate (PAA-Bdi), as well as di-, tetra-, and octamers of Galalpha1-->3Gal. All were tested for inhibitory activity by anti-alphaGal ELISA and complement-dependent cytotoxicity tests. PAA-Bdi was the best inhibitor of binding as well as cytotoxicity of anti-alphaGal antibodies. Monomeric oligosaccharides efficiently prevented binding of anti-alphaGal IgG, but less well that of anti-alphaGal IgM, with tri- and pentasaccharides showing a better efficacy than the disaccharide. The two trisaccharides Galalpha1-->3Galbeta1-->4GlcNAc and Galalpha1-->3Galbeta1-->3GlcNAc were equally effective. Oligomers of Galalpha1-->3Gal were more effective than monomers in blocking the binding of anti-alphaGal IgG. However, they could not block IgM binding, nor could they match the efficacy of PAA-Bdi. We conclude that oligosaccharides with terminal Galalpha1-->3Gal, most effectively as PAA-conjugates, can prevent binding and cytotoxicity of human anti-alphaGal in vitro. The PAA-Bdi conjugate might be most suited for use as a Sepharose-bound immunoabsorption material.

[Effect of synthetic fragments of immunodominant regions of HIV viral proteins on the oxygen metabolism of human neutrophils]. / Vliianie sinteticheskikh fragmentov immunodominantnykh raionov belkov VICh na kislorodnyi metabolizm neitrofilov cheloveka.

Influence of synthetic peptides identical to fragments of natural human immunodeficiency virus (HIV) glycoproteins gp 120 and gp 41, on luminol-enhanced chemiluminescence (CL) of human neutrophils has been studied. It was established that some of peptide analogs of gp 120 and gp 41 immunodominant regions are able to suppress spontaneous CL: but when being used with dimethylsulfoxide they dramatically stimulate it and deteriorate opsonized zymosan-induced CL. Conclusions about the necessity of possible side effects considering during use of peptide vaccines against HIV have been made. It is also possible to explain some neutrophil dysfunction in HIV infected subjects as the result of HIV glycoproteins direct influence on this cells.

[Study of the antigenic structure of hepatitis B virus proteins. I. Synthesis of pre-S fragments of hepatitis B virus proteins and their immunogenicity]. / Izuchenie antigennoi struktury belkov virusa gepatitaa B. I. Sintez fragmentov pre-S belkov virusa gepatita B i izuchenie ikh immunogennosti.

Fragments of hepatitis B virus envelope proteins corresponding to the parts of the pre-S domain were synthesised and immobilized on the carriers with low own immunogenicity. The highest stimulation of the antibody production was observed for the antigens immobilized on microspherical carriers or gelatin modified by H-Gly-Tyr-OH. Among peptides used for immunization, pre-S fragment 134-144, conjugated with microspherical carrier, proved to be the most active.

[Role of adrenergic mechanisms in the cerebrovascular effect of thyroliberin]. / Znachenie adrenergicheskikh mekhanizmov v tserebrovaskuliarnom éffekte tiroliberina.

Thyroliberin increases the cerebral blood flow both in anesthesized cats and unanesthetized rabbits under hemorrhagic shock. At the same time the increase of the arterial pressure is observed, caused by activation of the sympathoadrenal system. This is confirmed by experiments with the removal of the hypertensive reaction to thyroliberin after the use of the alpha-adrenoblockers. Analysis of the action mode of thyroliberin on the cerebral circulation with the use of atropine, dihydroergotoxin and propranolol allowed one to establish the involvement of beta-adrenoreceptors of the cerebral vessels in mediation of the cerebrovascular effect of the drug. The thyroliberin ability to improve the cerebral circulation under pronounced hypotension as well as to make the arterial pressure return to normal underlies its positive effect on the lifespan of animals under hemorrhagic shock.