An electrochemical detection method was applied to the determination of the synthetic peptide TP9201 (Telios Pharmaceuticals). The method utilizes reversed-phase HPLC, followed by post-column formation of Cu(II)-peptide complexes to render peptides electrochemically active via the Cu(III/II) couple. TP9201 is cyclic and N-amidated; the lack of a free amine precludes the use of typical fluorescent labeling reagents. Neither the cyclic structure nor the N-amidation prevented the copper complexation reaction, however. The detection limit in bovine serum was 20 nM, limited by interfering sample peaks, and the detector response was linear in a range 10-400 nM.
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http://dx.doi.org/10.1016/0731-7085(95)01623-6 | DOI Listing |
Stroke
June 2000
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Background And Purpose: Platelets become activated and accumulate in brain microvessels of the ischemic microvascular bed after experimental focal cerebral ischemia. The binding of glycoprotein IIb/IIIa (integrin alpha(IIb)beta(3)) on platelets to fibrinogen is the terminal step in platelet adhesion and aggregation. This study tests the hypothesis that inhibition of platelet-fibrin(ogen) interactions may prevent microvascular occlusion after experimental middle cerebral artery occlusion (MCA:O).
View Article and Find Full Text PDFStroke
September 1997
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0632, USA.
Background And Purpose: We examined the ability of TP-9201, a platelet glycoprotein IIb/IIIa receptor antagonist, to prevent carotid artery rethrombosis in the anesthetized dog.
Methods: Occlusive thrombosis was induced by electrolytic injury of the left carotid artery. Thirty minutes later, 0.
Am J Hematol
October 1996
School of Chemical Engineering, Georgia Institute of Technology Atlanta 30332-0100, USA.
Adherence of sickle erythrocytes to vascular endothelium likely initiates or participates in microvascular occlusion, leading to ischemic tissue and organ damage characteristic of sickle-cell pain episodes. In vitro, sickle-cell adherence to endothelium involves adhesive plasma proteins and integrin and nonintegrin receptors on sickle cells and endothelial cells. The involvement of arginine-glycine-aspartic acid (RGD) sequences in adhesive plasma proteins and integrin receptors suggests that RGD-containing peptides may inhibit sickle-cell/endothelial-cell adherence.
View Article and Find Full Text PDFBiochimie
January 1997
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co Ltd, Ibaraki, Japan.
We biochemically characterized a new disintegrin, flavostatin, isolated from Trimeresurus flavoviridis venom. Flavostatin inhibited ADP-, collagen-, and thrombin receptor agonist peptide-induced platelet aggregation in human platelet-rich plasma (IC50 range: 59 to 111 nM) and blocked the binding of biotinylated human fibrinogen to purified GPIIb/IIIa with an inhibitory potency 31,000-fold higher than that of Arg-Gly-Asp-Ser (RGDS). Flavostatin strongly inhibited high-shear-stress-induced platelet aggregation in platelet-rich plasma (PRP) with an IC50 value of 188 nM.
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