Characterisation of the Anticoagulant Properties of a Range of Structurally Diverse Sulfated Oligosaccharides

Wall, Dominic; Douglas, S.; Ferro, Vito; Cowden, W. B.; Parish, Christopher R.

doi:10.1016/s0049-3848(01)00314-0

Cited by 40 publications

(32 citation statements)

References 25 publications

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“…Although, the primary application for the acid hydrolysis of biomass is the production of raw material to obtain bioethanol, there are several biological activities related to oligosaccharides derived from molecules such as carrageenan, which may appear as other applications, such as antiviral (Katsuraya et al, 1999), antitumor (Yuan et al, 2006), anti-inflammatory (Sanders et al, 1999), anticoagulants (Wall et al, 2001) and antiangiogenic (Kãsbauer et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Kappaphycus alvarezii extract used for the seed treatment of soybean culture

Costa¹,

Alves²,

Alab³

et al. 2017

Afr. J. Agric. Res.

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Marine macroalgae, Kappaphycus alvarezii has economic importance which is considered as the main source of Kappa carrageenan, a hydrocolloid used in various industries as an emulsifying agent and stabilizer. In the production process of this raw material, the fresh seaweed is subjected to grinding and filtering process, yielding a wet solid fraction rich in carrageenan and other liquid fractions. The latter has been studied for its use in pulverization of bean leaves, wheat, soybean, rice, among others. Several reports have shown positive effects on the growth, yield and quality of vegetables and grains treated with the extract of this alga. However, there are few reports on the use of the liquid extract of K. alvarezii for seed treatment, and also of its use in conjunction with the solid fraction of seaweed. In this context, this study aims to evaluate the physiological quality of soybean seeds treated with liquid extract of this alga and, with the mixture of liquid extract and solid biomass, submitted to a hydrolysis process. Two soybean seed treatment tests were performed in laboratory: one treatment contained pure liquid extract (100%) while the other was mixed with two samples of solid biomass hydrolyzed with concentrations of 25 and 75%. For comparison of their results, there was a positive control treatment and one negative control treatment. The results showed that, within the present working conditions, treatments with seaweed extract can increase the length of the aerial part of the seedling up to 28% and the length of the primary root up to 19% as compared to the negative control; thus, it improves the physiological performance of seeds.

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Section: Introductionmentioning

confidence: 99%

Kappaphycus alvarezii extract used for the seed treatment of soybean culture

Costa¹,

Alves²,

Alab³

et al. 2017

Afr. J. Agric. Res.

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“…Their mechanism of action is proposed to be solely allosteric, by binding to HCII and triggering interaction of the NH 2 -terminal sequence with exosite I. The sulfated disaccharide, sucrose octasulfate (SOS), a known anti-ulcer drug (21) recently identified as an antitumor agent (22), exhibits moderate anticoagulant properties, measured by clotting assays (22,23). The present work describes the ϳ2000-fold accelerating effect of SOS on the inactivation of thrombin by HCII, demonstrates the involvement of thrombin exosite I, and…”

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confidence: 99%

Sucrose Octasulfate Selectively Accelerates Thrombin Inactivation by Heparin Cofactor II

Sarilla

Habib

Kravtsov

et al. 2010

Journal of Biological Chemistry

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) and HCII to exosite I. Meizothrombin(des-fragment 1), binding SOS with K D ‫؍‬ 1600 ؎ 300 M, and thrombin were inactivated at comparable rates, and an exosite II aptamer had no effect on the inactivation, suggesting limited exosite II involvement. SOS accelerated inactivation of meizothrombin 1000-fold, reflecting the contribution of direct exosite I interaction with HCII. Thrombin generation in plasma was suppressed by SOS, both in HCIIdependent and -independent processes. The ex vivo HCII-dependent process may utilize the proposed model and suggests a potential for oversulfated disaccharides in controlling HCII-regulated thrombin generation.The central coagulation proteinase, ␣-thrombin (T), 2 is covalently inactivated by the serpins antithrombin (AT) and heparin cofactor II (HCII), in reactions that are accelerated by sulfated glycosaminoglycans (GAGs) (1-6). Two electropositive sites on thrombin, exosites I and II, are differentially involved in its inactivation by HCII and AT (7,8). High molecular weight GAGs act as templates between thrombin exosite II and the GAG binding sites on AT and HCII (1, 2, 5, 9 -11), and an 18 saccharide unit length is required for template activity (12).The HCII mechanism also utilizes the allosteric interaction of thrombin exosite I with the Glu 53 -Asp 75 acidic sequence in the HCII NH 2 -terminal region that contains two hirudin-(54 -65)-like repeats (3,4,(13)(14)(15)(16)(17). This sequence, not present in AT, becomes available for thrombin interaction upon GAG binding of HCII (3,16). Direct evidence was provided by the crystal structure of the HCII⅐S195A-thrombin Michaelis complex, in which residues 56 -72 of HCII make contact with exosite I (16). Both repeats are required for heparin-and DS-catalyzed thrombin inactivation, as demonstrated by the decreased inhibitory potential of HCII NH 2 -terminal deletion mutants (3,14). Mutation of thrombin exosite I residues Arg 67 and Arg 73 resulted in significantly slower inactivation by native HCII (15). In reactions utilizing template-forming GAGs, both the template and allosteric interactions contribute to the mechanism by binding of GAG to thrombin exosite II and interaction of thrombin-complexed GAG with the heparin binding site in HCII, thereby triggering interaction of the HCII NH 2 -terminal sequence with exosite I. The intermediate T⅐GAG⅐HCII complexes, stabilized by two interactions, are significantly tighter than the T⅐GAG⅐AT complexes (9).Oligosaccharides shorter than 18 saccharide units, such as dermatan sulfate hexasaccharides, and sulfated bis-lactobionic and bis-maltobionic acid amides moderately accelerated inhibition by HCII but not [18][19][20]. These molecules are too small for template action, and it is unknown whether they bind to thrombin. Their mechanism of action is proposed to be solely allosteric, by binding to HCII and triggering interaction of the NH 2 -terminal sequence with exosite I. The sulfated disaccharide, sucrose octasulfate (SOS), a known anti-ulcer drug (21) recently identified as an antitumor...

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“…1 Human and mammalian toxicology studies demonstrate that PI-88 is welltolerated and has low anticoagulant activity. 3 PI-88 is currently in Phase II clinical trials to assess its therapeutic potential as an anticancer drug and is administered to patients by continuous infusion or repeated injection.…”

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confidence: 99%

Blockade of Vascular Smooth Muscle Cell Proliferation and Intimal Thickening After Balloon Injury by the Sulfated Oligosaccharide PI-88

Francis

Parish²,

McGarry³

et al. 2003

Circulation Research

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Abstract-Percutaneous transluminal coronary angioplasty is a frequently used interventional technique to reopen arteriesthat have narrowed because of atherosclerosis. Restenosis, or renarrowing of the artery shortly after angioplasty, is a major limitation to the success of the procedure and is due mainly to smooth muscle cell accumulation in the artery wall at the site of balloon injury. In the present study, we demonstrate that the antiangiogenic sulfated oligosaccharide, PI-88, inhibits primary vascular smooth muscle cell proliferation and reduces intimal thickening 14 days after balloon angioplasty of rat and rabbit arteries. PI-88 reduced heparan sulfate content in the injured artery wall and prevented change in smooth muscle phenotype. However, the mechanism of PI-88 inhibition was not merely confined to the antiheparanase activity of this compound. PI-88 blocked extracellular signal-regulated kinase-1/2 (ERK1/2) activity within minutes of smooth muscle cell injury. It facilitated FGF-2 release from uninjured smooth muscle cells in vitro, and super-released FGF-2 after injury while inhibiting ERK1/2 activation. PI-88 inhibited the decrease in levels of FGF-2 protein in the rat artery wall within 8 minutes of injury. PI-88 also blocked injury-inducible ERK phosphorylation, without altering the clotting time in these animals. Optical biosensor studies revealed that PI-88 potently inhibited (K i 10.3 nmol/L) the interaction of FGF-2 with heparan sulfate. These findings show for the first time the capacity of this sulfated oligosaccharide to directly bind FGF-2, block cellular signaling and proliferation in vitro, and inhibit injury-induced smooth muscle cell hyperplasia in two animal models. As such, this study demonstrates a new role for PI-88 as an inhibitor of intimal thickening after balloon angioplasty. The full text of this article is available online at http://www.circresaha.org. (Circ Res. 2003;92:e70-e77.)Key Words: phosphomannopentaose sulfate Ⅲ heparanase inhibitor Ⅲ smooth muscle cells Ⅲ neointima formation Ⅲ balloon angioplasty P hosphomannopentaose sulfate (PI-88) is a recently developed synthetic polysulfated oligosaccharide that inhibits the activity of the extracellular matrix-degrading enzyme heparanase. 1 PI-88 is a 2-kDa heparan sulfate mimetic structurally distinct from heparin, a heterogenous mixture of polysaccharide chains of varying length with a molecular weights of 3 to 30 kDa. PI-88 is also structurally and functionally different from small heparin-like polyaromatic anionic-type compounds 2 and other heparan sulfate mimetics. 1 In vivo studies have shown that PI-88 is a potent inhibitor of tumor metastasis and angiogenesis. 1 Human and mammalian toxicology studies demonstrate that PI-88 is welltolerated and has low anticoagulant activity. 3 PI-88 is currently in Phase II clinical trials to assess its therapeutic potential as an anticancer drug and is administered to patients by continuous infusion or repeated injection.Percutaneous transluminal coronary angioplasty (PTCA) is common...

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Characterisation of the Anticoagulant Properties of a Range of Structurally Diverse Sulfated Oligosaccharides

Cited by 40 publications

References 25 publications

Kappaphycus alvarezii extract used for the seed treatment of soybean culture

Kappaphycus alvarezii extract used for the seed treatment of soybean culture

Sucrose Octasulfate Selectively Accelerates Thrombin Inactivation by Heparin Cofactor II

Blockade of Vascular Smooth Muscle Cell Proliferation and Intimal Thickening After Balloon Injury by the Sulfated Oligosaccharide PI-88

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