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PubMed1986

Three-dimensional structure of favin: saccharide binding-cyclic permutation in leguminous lectins.

The three-dimensional structure of favin, the glucose- and mannose-binding lectin of Vicia faba (vetch, broad bean), has been determined at a resolution of 2.8 angstroms by molecular replacement. The crystals contain specifically bound glucose and provide the first high-resolution view of specific saccharide binding in a leguminous lectin. The structure is similar to those of concanavalin A (Con A) and green pea lectin; differences from Con A show that minimal changes are needed to accommodate the cyclic permutation in amino acid sequence between the two molecules. The molecule is an ellipsoidal dimer dominated by extensive beta structures. Each protomer contains binding sites for two divalent metal ions (Mn2+ and Ca2+) and a specific saccharide. Glucose is bound by favin in a cleft in the molecular surface and has noncovalent contacts primarily with two peptide loops, one of which contains several metal ion ligands. The specific carbohydrate-binding site is similar to that of Con A in location and general peptide folding, despite several differences in specific amino acid residues.

Concanavalin A↗
PubMed2006

Receptor-binding protein of Lactococcus lactis phages: identification and characterization of the saccharide receptor-binding site.

Phage p2, a member of the lactococcal 936 phage species, infects Lactococcus lactis strains by binding initially to specific carbohydrate receptors using its receptor-binding protein (RBP). The structures of p2 RBP, a homotrimeric protein composed of three domains, and of its complex with a neutralizing llama VH domain (VHH5) have been determined (S. Spinelli, A. Desmyter, C. T. Verrips, H. J. de Haard, S. Moineau, and C. Cambillau, Nat. Struct. Mol. Biol. 13:85-89, 2006). Here, we show that VHH5 was able to neutralize 12 of 50 lactococcal phages belonging to the 936 species. Moreover, escape phage mutants no longer neutralized by VHH5 were isolated from 11 of these phages. All of the mutations (but one) cluster in the RBP/VHH5 interaction surface that delineates the receptor-binding area. A glycerol molecule, observed in the 1.7-A resolution structure of RBP, was found to bind tightly (Kd= 0.26 microM) in a crevice located in this area. Other saccharides bind RBP with comparable high affinity. These data prove the saccharidic nature of the bacterial receptor recognized by phage p2 and identify the position of its binding site in the RBP head domain.

Amino Acid Sequence↗
PubMed1978

Antimalarial activity of saccharidic polymers of dapsone and sulfadimethoxine.

With the purpose of obtaining pro-drugs of dapsone and sulfadimethoxine, those chemotherapeutic agents were attached through covalent bonding to starch polymeric dialdehyde (Sumstar-190). The antimalarial activity of the two resulting compounds - the dapsone saccharidic polymer (PS6) and the sulfadimethoxine saccharidic polymer (PS7) - in mice experimentally inoculated with Plasmodium berghei was significantly increased with this molecular modification. Mice infected with malaria and kept without treatment together with others which received different doses of PS6 and PS7 were also partially or totally cured, possibly due to the ingestion of excrements containing the parent chemotherapeutic agents.

Animals↗
PubMed1976

Cell surface saccharides of Trypanosoma lewis i. II. Lectin-mediated agglutination and fine-structure cytochemical detection of lectin-binding sites.

Bloodstream (BSF) and culture forms (CF) of Trypanosoma lewisi were specifically agglutinated with the plant lectins concanavalin A (Con A), soybean agglutinin (SBA), wheat germ agglutinin (WGA), and fucose-binding protein (FBP). Lectin-mediated cell agglutination was inhibited, and reversed in the presence of specific lectin-binding saccharides. Cells were agglutinated randomly with all lectins suggesting a uniform distribution in the trypanosome cell surface of the lectin-binding saccharide ligands. The BSF and CF were not agglutinated with phytohaemagglutinin-M, phytohaemagglutinin-P, or influenza virions. Living trypsinized BSF, which lacked a surface coat, gave agglutination results with the lectins identical to those obtained with living intact BSF. Glutaraldehyde- or formalin-fixed intact and trypsinized BSF gave results similar to those obtained with living cells and SBA, WGA, and FBP. However, intact, fixed BSF gave much lower agglutination levels with Con A than trypsinized-fixed, living intact, or living trypsinized BSF cells. Intact and trypsinized living and fixed CF gave identical agglutination results with each of the lectins. Living and fixed cells treated extensively with the glycoside hydrolases alpha-amylase, dextranase, and neuraminidase gave results with the lectins identical to those obtained with untreated cells. Con A bound at the cell surface was visualized with an iron-dextran (Fe-Dex) conjugate. Dense iron marker particles were distributed randomly in the intact BSF surface coat. The Con A-bound Fe-Dex marker was present on the pellicular and flagellar membrane outer lamina of trypsinized BSF and intact CF cells. Horseradish peroxidase (HRPO)-diaminobenzidine (DAB) coupled reactions also were used to visualize surface-bound Con A. Dense Con A-HRPO-DAB deposits were present uniformly in the BSF surface coat, and on the membranes of trypsinized BSF and intact CF trypanosomes. SBA and WGA were conjugated to HRPO and these used in DAB-coupled reactions at the ultrastructure level. Results obtained with the HRPO-conjugated lectins were similar in surface localization and distribution to those obtained with the Con A-HRPO-DAB preparations. Treatment of BSF and CF with the several glycoside hydrolases produced no apparent enhanced or reduced reactivity for the lectins in any of the fine-structure cytochemistry experiments. The cumulative results indicate that ligands similar or identical to alpha-D-mannose, N-acetylgalactosamine, and N-acetylglucosamine, and alpha-L-fucose are constituents in the extracellular surface coat matrix of T. lewisi BSF. Similar conclusions also pertain to the pellicular and flagellar membrane ligands of the BSF and CF cells. Moreover, results obtained with the glycoside hydrolases and influenza virions suggest that the T. lewisi cell surface ligands are not associated directly with repetitively bonded alpha-I,4- and alpha-I,6-D-glucans or sialic acid moieties.

Acetylglucosamine↗
PubMed1989

Saccharide expression on wounded endothelial cell monolayers in vitro.

Monolayer cultures of porcine aortic endothelial cells were used as a model of the endothelium of large arteries. Linear wounds were produced in such cultures by scraping and the subsequent sequence of events in nearby cells was analysed. The earliest detectable event was cellular spreading at the margins of the wounds (2 h) followed by cell migration (starting at 6-8 h) and cell proliferation in regions adjacent to the wound (16 h and later). Cell spreading was associated with the appearance of saccharides selectively at the spreading margins of the cells, which bound the lectins, ConA, LCA and PSA, and were sensitive to alpha-mannosidase. Terminal alpha-mannosyl residues were therefore present. The appearance of these saccharides suggests a mechanism by which monocytes might adhere to and/or migrate through the endothelium of vessels at sites of cellular response to injury.

Animals↗
PubMed1987

Analyzing aversiveness of denatonium saccharide and quinine in rats.

Denatonium saccharide is reported to be the most bitter substance currently known. Two experiments comparing the suppressive capabilities of this compound and the more common bitter, quinine, are presented. Analysis indicated that rats preferred to consume denatonium rather than quinine when afforded a choice between the two. Exp. 2 also indicated that the pairing of quinine with vanilla and almond flavors resulted in subsequent refusal of these flavors. Pairing flavors with denatonium did not produce comparable refusals. Caution is expressed with regard to the use of denatonium saccharide as a rodent repellent.

Animals↗
PubMed2003

Effects of postexsanguination vascular infusion of cattle with a solution of saccharides, sodium chloride, and phosphates or with calcium chloride on quality and sensory traits of steaks and ground beef.

Grain-finished Hereford x Angus steers (n = 36) were assigned to one of three treatmentgroups. Immediately after jugular exsanguination, 12 steers were infused at 10% of live weight via the left carotid artery with a solution developed by MPSC, Inc. (St. Paul, MN) consisting of 98.52% water, 0.97% saccharides, 0.23% sodium chloride, and 0.28% phosphate blend (MPSC); 12 steers were infused at 10% of live weight with 0.30 M CaCl2 (CaCl2); and 12 steers were exsanguinated conventionally and served as noninfused controls (CON). Declines in pH for three muscles were measured. CaCl2-infused carcasses exhibited extensive muscle contraction at the time of cooler entry. Carcasses were graded at 24 h postmortem and fabricated at 48 h postmortem. Longissimus lumborum (LL), semitendinosus (ST), and quadriceps femoris (QF) muscles were removed, vacuum packaged, and stored at 2 degrees C until 14 d postmortem. Then, 2.54-cm-thick steaks were cut from the LL and ST for shear force and sensory evaluations. Ground beef was formulated from the QF to contain 20% fat. Steers infused with MPSC and CaCl2 had 4.0 and 2.3% higher dressing percentage points, respectively, than CON steers. Calcium concentrations of the LL muscle for CaCl2- and MPSC-infused carcasses, as well as the CON carcasses, were 892.0, 158.9, and 216.6 ppm, respectively. For the TB and longissimus thoracis muscles, pH decline was more rapid for CaCl2- and MPSC-infused carcasses than for CON carcasses, but there were no differences in 24-h pH. Warner-Bratzler shear force values were much higher (P < 0.05), and descriptive attribute sensory panel tenderness scores much lower (P < 0.05), for the LL from CaCl2-infused carcasses than for MPSC-infused and CON carcasses. Flavor intensity of the LL of CaCl2-infused carcasses was reduced (P < 0.05); however, overall tenderness and flavor of the ST were unaffected (P > 0.05) by CaCl2 infusion. Beef flavor identification, brown-roasted flavor, and bloody/serumy flavor were lowest and soapy/chemical flavor was highest (P < 0.05) for both freshly cooked and warmed-over LL from CaCl2-infused carcasses. There were no distinct meat quality advantages for infusing cattle with a solution of saccharides, sodium chloride, and phosphates. Infusion with 0.30 M CaCl2 increased dressing percentage, but caused severe muscle contraction early postmortem, decreased LL tenderness markedly, and reduced flavor of LL steaks and ground beef.

Animals↗
PubMed1999

Oral phosphate binders: phosphate binding capacity of iron (III) hydroxide complexes containing saccharides and their effect on the urinary excretion of calcium and phosphate in rats.

Phosphate binders that contain aluminum or calcium are frequently prescribed to treat hyperphosphatemia in patients with end-stage renal disease (ESRD), but an accumulation of aluminum can lead to encephalopathy, aluminum-related bone disease (ARBD) such as osteomalacia, anaemia, and resistance to erythropoietin, and calcium accumulation can lead to hypercalcaemia. High phosphate concentrations are reduced in vitro and in vivo by a phosphate adsorption pill, which is synthesized by hydrolyzing ferrous sulfate in the presence of saccharides, to form an iron (III)-saccharide complex that is acid resistant and binds phosphate greater than iron (III) hydroxide alone. Under in vitro conditions, containing 3.26 mg P/dL, the iron (III)-sucrose complex showed the highest phosphate adsorption capacity at pH 2 with artificial gastric juice, 58.9 mg P/g binder. For the 7 day in vivo study, 0% (Group 1), 1% (Group 2), 4% (Group 3), and 8% (Group 4) iron (III)-sucrose complex was admixed into the rodent chow by weight and fed to 15 male Wistar rats. The weight and volume of the feces and urine, and the calcium, iron, and phosphorus excretions in the feces and urine samples were monitored for any signs of irregularity. Total urine outflow was collected during a 24-h period to determine the amount of phosphate recovered, which indicates the ability of the phosphate binder to reduce gastrointestinal phosphate absorption. The fecal iron excretion was significantly effected by the amount of binder ingested throughout the study for Group 2 (p < 0.001), Group 3 (p < 0.01), and Group 4 (p < 0.001). The urinary calcium excretion (mg/rat/24-h) significantly increased by the 7th day for Group 2 (p < 0.05) and Group 4 (p < 0.01) in comparison to the control. Finally, after 7 days, there was a significant drop in the urinary phosphorus levels (mg P/rat/24-h) in a dose dependent manner for Group 2: from 7.82 +/- 1.46 to 1.98 +/- 0.10 mg P/rat/24-h (102 mg P/dL/24-h; p < 0.05); Group 3: from 6.70 +/- 1.14 to 0.16 +/- 0.09 mg P/rat/24-h (6.0 mg P/dL/24-h; p < 0.01); and Group 4: from 8.25 +/- 0.67 to 0.04 +/- 0.01 mg P/rat/24-h (0.9 mg P/dL/24-h; p < 0.01). The results show that this new adsorbent might provide an alternative to conventional aluminum and calcium containing phosphate-binding agents for combating hyperphosphataemia.

Administration, Oral↗
PubMedDate not supplied

Evaluation of several saccharides as osmotic agent for peritoneal dialysate.

OBJECTIVE: The carbonyl group of glucose reacts non-enzymatically with the amino group of protein to form advanced glycosylation end-products (AGEs). AGEs are found in the peritoneum of continuous ambulatory peritoneal dialysis patients, and this AGE formation is suspected to be one of the causes of impaired peritoneal function. In order to control AGE formation in the peritoneum, AGE formation and ultrafiltration in rats were examined with peritoneal dialysates using as osmotic agents saccharides that lack a carbonyl group, the saccharic acid lactobionate [molecular weight (MW) 358.30], the sugar alcohol maltitol (MW 344.32), and the nonreducing sugar nistose (MW 666.58). DESIGN: Bovine serum albumin (BSA) (25 mg/mL) was incubated with 18, 36, and 72 mg/mL maltitol, lactobionate, nistose, and glucose at 37 degrees C. After 3 or 6 weeks, amounts of furosine and N-(carboxymethyl) lysine were measured. A 20-mL intraperitoneal injection of a lactate-based dialysate (osmotic pressure 388 mOsm/kg) containing 4.34% maltitol, 4.52% lactobionate, or 8.4% nistose was given to Sprague-Dawley rats and, after 2, 4, or 6 hours, the quantity of effluent and levels of urea nitrogen and creatinine in the effluent and in serum were measured. RESULTS: No increases in furosine or N-(carboxymethyl) lysine were seen with maltitol, lactobionate, or nistose after 3 and 6 weeks of incubation with BSA; AGE formation was not observed. In the study in rats, the quantity of abdominal fluid after a 6-hour dwell was nistose > lactobionate > maltitol > glucose. No differences in dialysate-to-plasma ratios for urea nitrogen or creatinine were seen in any group. CONCLUSIONS: AGE formation in peritoneal tissue might be controlled by using saccharides with a modified carbonyl group as osmotic agents for peritoneal dialysates. Nistose is considered to yield the most efficient dialysis.

Animals↗
PubMed2001

Oxidation and base-catalyzed elimination of the saccharide portion of GSLs having very different polarities.

Glycosphingolipids (GSLs), present in cell membranes, participate in a variety of biological functions. Although their exact role(s) may not be understood, it has been shown that 1) embryos lacking glucosylceramide synthase activity do not develop normally, 2) GSLs can affect neuritogenesis, and 3) they can function as receptors for some pathogens. To study the role of the saccharide portion of a GSL in any of these functions, it is necessary to either isolate it from the intact GSL or synthesize it. Because syntheses are more complex, modifications were made to the oxidation/elimination procedure previously described for the isolation of the saccharide portion of GM1 and GD1a to enable it to be used with GSLs of varying polarity. The key is to use a mixture of GSLs that differ in polarity. This appears to eliminate problems encountered when purified GSLs such as sulfatide or GT1b are used.

Animals↗
PubMed1989

Incorporation of measured photosynthetic rate in a mathematical model for calculation of non-structural saccharide concentration.

A simple mathematical model for calculating the concentration of mobile carbon skeletons in the shoot of soya bean plants [Glycine max (L.) Merrill cv. Ransom] was built to examine the suitability of measured net photosynthetic rates (PN) for calculation of saccharide flux into the plant. The results suggest that either measurement of instantaneous PN overestimated saccharide influx or respiration rates utilized in the model were underestimated. If neither of these is the case, end-product inhibition of photosynthesis or waste respiration through the alternative pathway should be included in modelling of CH2O influx or efflux; and even if either of these is the case, the model output at a low coefficient of leaf activity indicates that PN still may be controlled by either end-product inhibition or alternative respiration.

Carbohydrate Metabolism↗
PubMed2000

[Preparation of galactosyl-insulin with double saccharide density and a study of its hepatic targeting property].

This study was intended to improve the technical procedure so as to increase the saccharide density of galactosyl-recombinant insulin and elevate its liver targeting property. Using a branched compound 3,5-dihydroxy benzoic acid as the base of a conjugating bridge, the authors prepared a new double galactosyl-recombinant insulin, whose saccharide density being two times as high as that of galactosyl-recombinant insulin. The double gal-insulin conjugate, gal-insulin conjugate and original insulin were labeled with 131I, and then the three kinds of 131I labeled compounds were tested in rabbit whole body imaging to measure their properties of liver targeting. The peak values of rabbit liver concentration for double gal-insulin, gal-insulin and original insulin were 59.5%, 43.8% and 21.5%, respectively. These results demonstrate that for elevating the liver targeting property of galactosyl-recombinant compounds, a branched agent like 3,5-dihydroxyl benzoic acid can be adopted as an effective medium.

Animals↗
PubMed2002

[Separation of saccharides in tobacco by capillary zone electrophoresis].

A method for the separation of derivatized saccharides in tobacco with high performance capillary electrophoresis and ultraviolet spectrophotometry (HPCE-UV) is presented. Five saccharides in tobacco were derivatized with p-aminobenzonitrile, separated at pH 10.5 with 50 mmol/L borate buffer containing 5% (volume fraction, the same in the following percentage concentration) methanol, 5% acetonitrile, 2.5% ethyleneglycol, 2.5% 2-propanol and 1 mmol/L sodium dodecyl sulfate, and detected at 285 nm.

Electrophoresis, Capillary↗
PubMedDate not supplied

[Distribution of saccharide residues in glycoconjugates of the kidney in Gallus domesticus using peroxidase-conjugated lectins].

A battery of seven different horseradish-peroxidase labelled lectins (DBA, PNA, SBA, UEA I, WGA, ConA, LTA) was used to study the distribution of sugar residues in the glycoconjugates along the nephron and the collecting duct of the kidney of Gallus domesticus. As far as the glomerular components are concerned, we have demonstrated that the podocytes and, with a lesser extent, the mesangial cells are characterised by the presence of D-mannose, D-galactose-(beta 1- greater than 3)-N-acetyl-D-galactosamine and sialic acid. The glomerular capillary wall shows the presence of the disaccharide D-galactose-(beta 1- greater than 3)-N-acetyl-D-galactosamine and sialic acid. With regards to the tubules, the proximal tubule, the descending limb of the loop of Henle, the connecting tubule and the collecting one, are characterised by N-acetyl-D-galactosamine, (1- greater than 6)-alpha-L-fucose, D-mannose, N-acetyl-D-galactosamine and D-galactose-(beta 1- greater than 3)-N-acetyl-D-glucosamine. The cells of the connecting and collecting ducts show the presence of intracellular sialic acid, found also as component of the mucous secretion. The ascending limb of the loop of Henle and the distal tubule contain only three saccharidic residues, i.e. (1- greater than 6)-alpha-L-fucose, D-mannose and N-acetyl-D-glucosamine. Lectin histochemistry was also useful to define the saccharidic components of the mucus, which is normally present within the connecting and collecting ducts of the kidney of the birds. The cellular variability of the connecting and the collecting ducts is similar to that found in the kidney of some mammals. Such a variability seems to suggest a possible cell specialization along a single kidney tubule.

Animals↗
PubMed1985

Saccharide structures of the mouse embryo during the first eight days of development. Inferences from immunocytochemical studies using monoclonal antibodies in conjunction with glycosidases.

Monoclonal anti-carbohydrate antibodies have been used in conjunction with glycosidases in immunofluorescence studies to derive information about the structures and in situ distribution of saccharides of the mouse embryo during the first 8 days of development. The salient findings are as follows: Branched poly-N-acetyllactosamine sequences of I-antigen type are detectable from the first day onwards and are widely distributed in cells of the endoderm, ectoderm and mesoderm. Linear poly-N-acetyllactosamine sequences of i-antigen type are detectable from the fifth day onwards in cells of all three lineages, but have a more restricted distribution than the sequences of I-type. Poly-N-acetyllactosamine sequences that are susceptible to digestion with endo-beta-galactosidase are the main carriers of the SSEA-1, C14 and the blood group B-like antigens, which have the following structures (Formula; see text) and are found in endoderm and ectoderm but not in mesoderm cells. In the trophoblast however, these antigens are borne on saccharides that are resistant to endo-beta-galactosidase. A proportion of the poly-N-acetyllactosamine structures in the endoderm and the ectoderm of the 5- and 6-day embryos may contain the following novel structures: (Formula; see text) in which antigenicities of SSEA-1 and C14 determinants are masked. There are several types of sialyl-oligosaccharides: those reactive with anti-Gd, which has a specificity for NeuAc alpha 2-3Gal beta 1-4GlcNAc sequence in the extraembryonic mesoderm and the heart; those reactive with anti-Pr2 but not with anti-Gd, which may correspond to other N-acetylneuraminic acid containing sequences such as NeuAc alpha 2-3Gal beta 1-3GalNAc or NeuAc alpha 2-6Gal in preimplantation embryos and in the yolk sac, neural ectoderm and mesenchyme of the 8-day embryo; those with other sialic acid forms or linkages that do not react with anti-Gd and Pr2; among these are sialosyl-i sequences in the extraembryonic ectoderm, and sialosyl-I sequences in most cell types during the first 8 days. The latter are the main poly-N-acetyllactosamine structures in the neural ectoderm of the 8-day embryo. The sequence Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc/GlcNAc, or cross-reactive structures, which bind FC10.2 antibody occur in the extraembryonic endoderm and yolk sac. The roles of specific carbohydrate structures as receptors during embryonic development and cell growth are important topics of current research.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Effect of modification of membrane saccharides on hormonal imprinting in Tetrahymena.

Concanavalin-A (Con-A) competes with insulin for the insulin binding sites of the receptor, an event resulting in overlapping bonds. If the saccharide components of the receptor are subjected to periodate treatment the binding of insulin decreases and so does the imprinting evoked by it. Simultaneously, the binding of Con-A increase immediately after the treatment and 24 hours following the insulin imprinting. This phenomenon indicates that though the two ligands (i.e. insulin and Con-A) overlap on the intact receptor, alterations in the saccharide component influence their binding though not in the same manner and not in the same direction. Periodate treatment, similarly as observed in mammalian lymphocyte cultures, enhanced the division of Tetrahymenas and the peak of Con-A binding occurred parallel to the peak of division after periodate treatment of equal duration. Periodate treatment disturbed not only the binding of Con-A but that of other lectins as well. It has been concluded that hormonal imprinting requires a physiological condition of the membrane and any disturbance of the membrane will lead to a decrease in the efficacy of imprinting.

Carbohydrates↗
PubMed1978

Binding and functional properties of concanavalin A and its derivatives. II. A proteolytic product with saccharide-binding activity.

Limited digestion of the intact subunit of concanavalin A (Mr = 26,000) with trypsin followed by affinity chromatography on Sephadex G-100 has yielded a highly purified product designated here as Tn-Con A. Chemical studies have shown that Tn-Con A is composed of several components: a large fragment (Tn I, Mr = 19,000) spanning residues 1 to 172, and lower molecular weight polypeptides that are noncovalently associated with Tn I to form the active molecule. The molecular weight of Tn-Con A at pH 7 was 90,000, suggesting that, like native concanavalin A, it was a tetramer at physiological pH. Equilibrium dialysis experiments showed that Tn-Con A bound 1 molecule of alpha-methyl-D-glucoside/22,000 g atoms of protein and therefore that four saccharides are bound by the tetrameric molecule. Tn-Con A and native concanavalin A competed for the same receptors on the lymphocyte surface. Moreover, Tn-Con A was mitogenic for both mouse and human lymphocytes with dose-response curves similar to those of the native lectin. All of these results indicate that tryptic hydrolysis of concanavalin A produces a fragmented molecule retaining the saccharide-binding, subunit association, and mitogenic capacity of the native protein.

Amino Acids↗
PubMed1986

Neutralization of heparin-related saccharides by histidine-rich glycoprotein and platelet factor 4.

Heparin and heparin oligosaccharides prepared by nitrous acid depolymerization were fractionated by affinity chromatography on immobilized antithrombin and by gel chromatography. The anticoagulant activities of high affinity heparin of Mr greater than or equal to 7,800 could be readily neutralized by the plasma protein histidine-rich glycoprotein (see also Lijnen, H.R., Hoylaerts, M., and Collen, D. (1983) J. Biol. Chem. 258, 3803-3808), whereas oligosaccharides falling below 18 saccharide units (Mr 5,400) became increasingly resistant to neutralization. An octasaccharide with characteristic marked ability to accelerate the inactivation of Factor Xa by antithrombin retained greater than 50% of its activity even at a histidine-rich glycoprotein/oligosaccharide molar ratio of 500:1. Histidine-rich glycoprotein, like the platelet-derived heparin neutralizing protein platelet factor 4 (Lane, D.A., Denton, J., Flynn, A.M., Thunberg, L. and Lindahl, U. (1984) Biochem J. 218, 725-732), therefore requires interaction with saccharide sequences in addition to the antithrombin-binding pentasaccharide of heparin in order to efficiently express its antiheparin activity. Heparan sulfate isolated from pig intestinal mucosa (HS I, Mr approximately 20,000) and from human aorta (HS II, Mr approximately 40,000) exhibited anti-Factor Xa activities of 180 and 20 units/micromol [corrected], respectively. A fraction corresponding to about 5% of HS I bound with high affinity to immobilized antithrombin and contained all of the anticoagulant activity of the starting material. While these heparan sulfates were readily neutralized by platelet factor 4, they were relatively resistant to neutralization by histidine-rich glycoprotein, although complete neutralization could be attained in the presence of molar excess of this protein. These findings may be of importance in relation (a) to the functional role of endogenous anticoagulant polysaccharides at the vascular wall and (b) to clinical situations in which heparin or heparin-related compounds are administered as exogenous anticoagulants.

Heparin↗