An Investigation of the Functional Role of the Carboxylic Groups of Heparin Affinity for Antithrombin III and Anti-Xa Activity of Selectively Carboxyl Esterified Heparin

Mardiguian, J; Trillou, M

doi:10.1055/s-2007-1004356

Semin Thromb Hemost

1985

DOI: 10.1055/s-2007-1004356

|View full text |Cite

An Investigation of the Functional Role of the Carboxylic Groups of Heparin Affinity for Antithrombin III and Anti-Xa Activity of Selectively Carboxyl Esterified Heparin

J Mardiguian¹,

M Trillou²

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

1987

1994

Publication Types

Select...

Article2

Relationship

Self Cite0

Independent2

Authors

Journals

Cited by 2 publications

(1 citation statement)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many attempts to chemically modify heparin are reported in literature [3][4][5][6][7] which involve various reactive sites such as the hydroxyl, carboxyl and amino groups. In particular, heparin was covalently bound to many materials in attempts to improve the hemocompatibility.…”

mentioning

confidence: 99%

Chemical Modifications of Heparin.1: Reaction of Partially N-Desulfated Heparin with Glutaraldehyde

Diancourt

Braud

Vert

1994

Journal of Bioactive and Compatible Polymers

View full text Add to dashboard Cite

Purified glutaraldehyde was allowed to react with the primary amino groups generated by mild acidolysis of glucosamine N -sulfamino residues present in heparinic acid. The reaction yielded high molecular mass heparinoids (HMMHEP) or hydrogels, depending on experimental conditions. It was shown that a selected HMMHEP exhibited a higher anticoagulant activity than the starting heparin or the parent partially N -desulfated heparin. This HMMHEP degraded slowly in vitro in an aqueous medium buffered at pH = 7.4. Moreover, HMMHEP was biologically active after i.v. injection but not after s.c. and i.m. injections. Hydrogels also degraded slowly to yield biologically active higher molecular mass heparinoid. These findings suggested that neither N -desulfation nor coupling of glutaraldehyde adducts affected in a large extend the activity of the parent heparin.

show abstract

mentioning

confidence: 99%

Chemical Modifications of Heparin.1: Reaction of Partially N-Desulfated Heparin with Glutaraldehyde

Diancourt

Braud

Vert

1994

Journal of Bioactive and Compatible Polymers

View full text Add to dashboard Cite

show abstract

Probing the heparin‐binding domain of human antithrombin III with V8 protease

Liu

Chang

1987

European Journal of Biochemistry

View full text Add to dashboard Cite

From structural analysis on genetically abnormal and chemically modified human antithrombin Ill [Koide, T., Odani, S., Takahashi, K., Ono, T. and Sakuragawa, N. (1984) Proc. Natl Acad. Sci. USA 81,[289][290][291][292][293] Chang, J.-Y. and Tran, T. H., (1986) J. Biol. Chem. 261, 1174-1176Blackburn, M. N., Smith, R. L., Carson, J. and Sibley, C. C. (1984) J . Biol. Chem. 259,, the heparin-binding site of antithrombin 111 has been suggested to be in the region of Pro-41, Arg-47 and Trp-49. In this study the heparin-binding site was probed by preferential cleavage of V8 protease on heparin-treated and non-treated native antithrombin 111. The study has been based on the presumption that the heparin-binding site of antithrombin 111 is situated at exposed surface domain and may be preferentially attacked during limited proteolytic digestion. Partially digested antithrombin I11 samples were monitored by quantitative amino-terminal analysis and amino acid sequencing to identify the preferential cleavage sites. 1-h-digested antithrombin 111 was separated on HPLC and peptide fragments were isolated and characterized both qualitatively and quantitatively. The results reveal that Glu-Gly (residues 34 -39, Glu-Ala (residues 42-43) and Glu-Leu (residues 50-51) are three preferential cleavage sites for V8 protease and their cleavage, especially the Glu-Ala and the Glu-Leu sites, was drastically inhibited when antithrombin 111 was preincubated with heparin. Both high-affinity and low-affinity antithrombin-111-binding heparins were shown to inhibit the V8 protease digestion of native antithrombin 111, but the high-affinity sample exhibited a higher inhibition activity than the low-affinity heparin. These findings (a) imply that the segment containing residues 34-51 is among the most exposed region of native antithrombin I11 and (b) support the previous conclusions that this region may play a pivotal role in the heparin binding.The plasma glycoprotein, antithrombin 111, regulates the blood-blotting system by inhibiting a number of hemostatic proteases, such as thrombin and factors IXa, Xa, XIa and XIIa. These reactions are greatly accelerated by the polysaccharide heparin [l -31. Elucidation of the molecular basis for the inhibitory action of antithrombin I11 in the presence of heparin has been complicated by the fact that heparin binds not only to antithrombin 111 but also with the cognate enzymes like thrombin and factor IXa [l, 41. Different models have been proposed to account for the mechanism of heparin function [5 -141. One model that has been studied in detail showed that heparin combines with antithrombin 111 to induce conformational change for more competent inhibitory function [15 -201. The heparin -antithrombin-111 complex is apparently formed by the electrostatic interaction between the acidic groups (mostly sulfate) of heparin [9, 211 and the Lys/ Arg residues of antithrombin 111 122 -281 the region including Pro-41, Arg-47 and Trp-49 could be the potential heparin-binding site of antithrombin 111.In this paper ...

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

An Investigation of the Functional Role of the Carboxylic Groups of Heparin Affinity for Antithrombin III and Anti-Xa Activity of Selectively Carboxyl Esterified Heparin

Cited by 2 publications

References 1 publication

Chemical Modifications of Heparin.1: Reaction of Partially N-Desulfated Heparin with Glutaraldehyde

Chemical Modifications of Heparin.1: Reaction of Partially N-Desulfated Heparin with Glutaraldehyde

Probing the heparin‐binding domain of human antithrombin III with V8 protease

Contact Info

Product

Resources

About