Heparin interactions

Heparin, as described in Section 6, is an anionic, mucopolysaccharide, which is known to complex with, for example, other di- and polyamines. A spectral shift of 90 A has been reported for its adduct with the cationic 

Conductivity minima which have been reported for the interactions of quaternary ammonium compounds have been ascribed to associations which lower the critical micelle concentration and thus reduce the concentration of the substituted ammonium ions. Such an effect is considered to be somewhat unlikely in the present case because the chlorpromazine con- 

FIGURE 10, Phoreograms of the heparin-chlor-promazine HCI interaction 200 units/ml of heparin 10 Af chlorpromazine hydrochloride both in aqueous solution Gold electrodes 17°C. The values of the conductance G, in millimho, refer to the right-hand ordinate scale, while capacitance values, C, in nF, are scaled on the left. The phoreogram as well as the capacitance plot show well-defined minima. The linear base lines, which would be followed in the absence of a charge carrier interaction, are also indicated. 

The spectra show a displacement of the chlorpromazine peak at 3080-3100 A. While this slight bathochromic shift could be interpreted as evidence for the formation of a contact charge transfer complex, by itself it is not thought to be sufficient evidence. If heparin as an electron acceptor is forming a charge transfer complex with the strong electron donor chlorpromazine, a conductivity maximum should result. The opposite occurs. The role of hydrophobic bonding in the association should be considered. 

Whatever the mechanism, a pharmaceutical incompatibility between sodium heparin and chlorpromazine hydrochloride solutions is confirmed. The clinical significance of an interaction between the two drugs after administration has not been demonstrated. The type of electrode reaction demonstrated in the model in vitro system may occur in vivo, because a biological membrane has been shown to be capable of acting as an electrode and it known that heparin is taken up by cell membranes. Binding of chlorpromazine to other mucopolysaccharides may be of significance in the pharmacokinetic disposition of the drug. 

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Essentially as a result of its ability to bind to basic sites, heparin interacts with many proteins.398 Although most of these interactions (such as that with protamine, a basic protein frequently used to neutralize heparin399) are probably not of biological significance, binding to plasma proteins and to proteins exposed on the surface of endothelial cells has an important influence on the circulation system. 

Tyler-Cross, R., M. Sobel, L.E. McAdory, and R.B. Harris. 1996. Structure-function relations of antithrombin Ill-heparin interactions as assessed by biophysical and biological assays and molecular modeling of peptide-pentasaccharide-docked complexes. Arch Biochem Biophys 334 206-213. 

S Faham, RJ Linhardt, DC Rees. Diversity does make a difference fibroblast growth factor—heparin interactions. Curr Opin Struct Biol 8 578—586, 1998. 

In keeping with a high amount of non-ionic contact in the bFGF/heparin interaction is the recent and interesting finding that non-sulfated heparan-derived... 

T14. Heparin Interactions Heparin, a highly negatively charged glycosaminoglycan, is used clinically as an anticoagulant. It acts by binding several plasma proteins,... 

The anticoagulant activity of heparin is endowed by its ability to form strong complexes with a variety of blood clotting factors and thus neutralize their action. For instance, heparin interacts with thrombin, fibrinogen, prothrombin, factors IX-XII... 

Walters MI, Roberts WH. Gentamicin/heparin interactions effects on two immunoassays and on protein binding. Ther Drug Monit 1984 6(2) 199-202. 

Heparin has been used in enzyme purification such as recombinant human mast cell tryptase. The purified enzyme is fully active [12]. Heparin-based affinity chromatography also permitted the isolation of growth factors such as basic fibroblast growth factor (bFGF). The affinity is lower when bFGF is complexed with acidic gelatin [13]. The elution of synthetic TFPI (tissue factor pathway inhibitor) peptidic fragments on immobilized heparin has allowed one to find the peptidic sequence responsible for the TFPI-heparin interaction [14]. 

Z. Y. Ye, R. Takano, K. Hayashi, T. V. Ta, et al., Structural requirements of human tissue factor pathway inhibitor (TFPI) and heparin for TFPI-heparin interaction, Throm. Res. 89 263 (1998). 

Hileman RE, Jennings RN, Linhardt RJ. Thermodynamic analysis of the heparin interaction with a basic cyclic peptide using isothermal titration calorimetry. Biochemistry 1998 37 15231-15237. 

No stoichiometry can be assigned to the heparin interactions because of the uncertainty of the exact composition of commercial solutions of this drug. 

PEC of chitosan and heparin have been also studied as matrices for wound healing, because it has been demonstrated that heparin interacts and stabilizes growth factors involved in the wound healing process [ 152]. 

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