Preparation, structure and anticoagulant activity of a low molecular weight fraction produced by mild acid hydrolysis of sulfated rhamnan from Monostroma latissimum.

A low molecular weight fraction, designated LMWP, was prepared by mild acid hydrolysis of sulfated rhamnan from Monostroma latissimum and purified by anion-exchange and gel-permeation chromatography. Chemical and spectroscopic analyses showed that LMWP was mainly composed of rhamnose, and its molecular weight was about 33.6 kDa. The backbone of LMWP consists of 1,3-linked α-L-rhamnose units with partially sulfate groups at the C-2 position. Approximately 25% of 1,3-linked α-L-rhamnose units is substituted at C-2 by sulfated or non-sulfated 1,3-linked α-L-rhamnose and 1,2-linked α-L-rhamnose units. LMWP effectively prolonged clotting time as evaluated by the activated partial thromboplastin time assay and was a potent thrombin inhibitor mediated by heparin cofactor II. The investigation demonstrated that LMWP is a novel sulfated polysaccharide with anticoagulant activity.

[Alkylating derivatives of 2-amino-2-deoxysugars and 1-methylamino-1-deoxypolyols (synthesis and experimental study)]. / Alkiliruiushchie proizvodnye 2-amino-2-dezoksisakharov i 1-metilamino-1-dezoksipoliolov (sintez i éksperimental'noe izuchenie).

A number of derivatives of 2-amino-2-deoxysaccharides and 1-methylamino-1-deoxypolyols acylated by cytotoxic phenylalkanic and amino acids were synthesized and experimentally tested for antitumor activity. Some compounds showed a high antitumor activity against plasmacytoma MOPC-406: a 2-fold increase in experimental animals survival and a 80--100% cure rate were observed. Physicochemical properties, particularly, stability in aqueous solution and antitumor activity of one of the most potent compounds--1-methylamino-1-deoxy-1-N[p-di(2-chloroethyl) aminophenylacetyl]-D-glucitol (Agluphen)--are described in detail.

Synthesis of 4-deoxy-D-xylo-hexose and 4-azido-4-deoxy-D-glucose and their effects on lactose synthase.

Syntheses are reported of 4-deoxy-D-xylo-hexose and 4-azido-4-deoxy-D-glucose as potential inhibitors for lactose synthase [uridine 5'-(alpha-D-galactopyranosyl pyrophosphate):D-glucose 4-beta-D-galactopyranosyltransferase, EC 2.4.1.22]. These syntheses involved SN2 displacement of the 4-methylsulfonyloxy group of methyl 2,3,6-tri-O-benzoyl-4-O-methylsulfonyl-alpha-D-galactopyranoside by iodide and azide ions. In both cases, inversion in configuration was observed. The resulting intermediates, methyl 2,3,6-tri-O-benzoyl-4-deoxy-4-iodo-alpha-D-glucopyranoside and methyl 4-azido-2,3,6-tri-O-benzoyl-4-deoxy-alpha-D-glucopyranoside, were obtained in crystalline form. Both 4-deoxy-D-xylo-hexose and 4-azido-4-deoxy-D-glucose were found to be inhibitors for lactose synthase in the presence of alpha-lactalbumin, but had no effect in the absence of alpha-lactalbumin. Both D-glucose analogues bind to the enzyme system far more weakly than D-glucose, suggesting that the recognition of the 4-OH group of the acceptor substrate is an important factor in binding.