Molecular and biochemical profiling of a heparin-derived oligosaccharide, C3.
This study was designed to characterize a heparin-derived oligosaccharide (HDO), C3, using chemical and biochemical methods. Although previous studies have suggested C3 as a promising compound in the treatment of Alzheimer's disease (AD), its molecular and biochemical properties are still unknown. In this study, the molecular profiles and anticoagulant effects of C3 were investigated. To characterize the molecular and biochemical properties of C3, gel permeation chromatography (GPC), polyacrylmide gel electrophoresis (PAGE), radiolabeling and anticoagulant assays, such as activated partial thromboplastin time (APTT), Heptest, and anti-factor Xa assay, were used. The GPC profile revealed that C3 was an ultra-low-molecular-weight (MW) heparin mixture. The multiple components in C3 were studied with PAGE analysis. Tritium-labeled C3 exhibited similar biological properties as nonlabeled materials. The biological assays showed that C3 and its components exhibited weak anticoagulant effect. These results demonstrated the applicability of the combination of GPC, PAGE, and coagulation assays to characterize the molecular and biochemical profile of HDO. In addition, the low anticoagulant effect of C3 suggests that this compound could be a relatively low-risk adjunct in the treatment of AD.
Ma
Qing
Q
Department of Pharmacology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
Dudas
Bertalan
B
Daud
Asif
A
Iqbal
Omer
O
Hoppensteadt
Debra
D
Jeske
Walter
W
Cornelli
Umberto
U
Lee
John
J
Lorens
Stanley
S
Mervis
Ronald
R
Hanin
Israel
I
Capila
Ishan
I
Linhardt
Robert
R
Fareed
Jawed
J
D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001780:Blood Coagulation Tests; D004591:Electrophoresis, Polyacrylamide Gel; D065427:Factor Xa Inhibitors; D006493:Heparin / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008970:Molecular Weight; D009844:Oligosaccharides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D010314:Partial Thromboplastin Time; D014316:Tritium
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009844:Oligosaccharides; D014316:Tritium; D006493:Heparin