[Synthesis of low molecular weight mimetics of heparin].

Natural hexosaminoglycan heparin remains the most commonly prescribed anticoagulant in hospitalized patients. However its administration could induce side clinical events, including thrombocytopenia and bleeding. This explaines the need of development of alternative anticoagulant drugs based on modified heparin and polyanionic oligo- and polysaccharide derivatives, such as sulfated glucans, phosphomannans and fucoidans. Here we review the works on the synthesis of oligosaccharides related to low molecular weight hepain fragments and their derivatives, as well as oligosaccharides, which imitate parts of heparin chain responsible for biological activity. These works were aimed to develop the pharmaceutical preparations lacking ofheparin disadvantages.

[Anticoagulant activity of fucoidans from brown algae].

The anticoagulant activity of polysaccharide fucoidans from 11 species of brown algae was studied. The anticoagulant activity was measured by the activated partial thromboplastin time (APTT), prothrombin time and thrombin time. Inhibitory action of fucoidans varied significantly from one species to another. Fucoidans from Laminaria saccharina and Fucus distichus showed high anticoagulant activities, while fucoidans from Cladosiphon okamuranus and Analipus japonicus were almost inactive. The fucoidan inhibitory effect on thrombin and factor Xa in the presence or in the absence of natural thrombin inhibitor, antithrombin III (AT III), was also studied. In contrast to the best studied anticoagulant heparin the most of the fucoidans inhibited thrombin in the absence of AT III. In the presence of AT III inhibitory effect of fucoidans was increased considerably. Unlike heparin, the effect of fucoidans on factor Xa was very weak in the presence of AT III and was not observed in the absence of AT III. The correlation between the anticoagulant activities of this series of fucoidans and their anti-inflammatory action, studied by us earlier, was not found. It is expected that two these types of fucoidan activities depend on different structural features of fucoidans. These findings show the possibility to obtain fucoidans with high anti-inflammatory action and with low anticoagulant activity. Anticoagulant activity of the fucoidans did not depend on the content of fucose, the other neutral sugars and sulfates in the preparations, and also on the structure of the backbone of molecule. Taken together, these results indicate on prospects of fucoidan study as potential therapeutic agents.

[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.