Synthesis and Anticoagulant Activity of Polyureas Containing Sulfated Carbohydrates

被引：46

作者：

Huang, Yongshun ^{[1
]}

Shaw, Maureen A. ^{[3
]}

Mullins, Eric S. ^{[3
]}

Kirley, Terence L. ^{[4
]}

Ayres, Neil ^{[1
,2
]}

机构：

[1] Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA

[2] Univ Cincinnati, Mat Sci & Engn Program, Cincinnati, OH 45221 USA

[3] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA

[4] Univ Cincinnati, Dept Pharmacol & Cell Biophys, Coll Med, Cincinnati, OH 45267 USA

来源：

BIOMACROMOLECULES | 2014年 / 15卷 / 12期

基金：

美国国家科学基金会;

关键词：

GLYCOSAMINOGLYCAN-MIMETIC BIOMATERIALS; HEPARIN-INDUCED THROMBOCYTOPENIA; ANTITHROMBIN-III; COVALENT IMMOBILIZATION; BLOOD COMPATIBILITY; GLYCOPOLYMERS; ADSORPTION; POLYURETHANES; PLASMA; HEMOCOMPATIBILITY;

D O I：

10.1021/bm501245v

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Polyurea-based synthetic glycopolymers containing sulfated glucose, mannose, glucosamine, or lactose as pendant groups have been synthesized by step-growth polymerization of hexamethylene diisocyanate and corresponding secondary diamines. The obtained polymers were characterized by gel permeation chromatography, nuclear magnetic resonance spectroscopy, and Fourier transform infrared spectroscopy. The nonsulfated polymers showed similar results to the commercially available biomaterial polyurethane TECOFLEX in a platelet adhesion assay. The average degree of sulfation after reaction with SO3 was calculated from elemental analysis and found to be between three and four -OSO3 groups per saccharide. The blood-compatibility of the synthetic polymers was measured using activated partial thromboplastin time, prothrombin time, thrombin time, anti-IIa, and anti-Xa assays. Activated partial thromboplastin time, prothrombin time, and thrombin time results indicated that the mannose and lactose based polymers had the highest anticoagulant activities among all the sulfated polymers. The mechanism of action of the polymers appears to be mediated via an anti-IIa pathway rather than an anti-Xa pathway.

引用

页码：4455 / 4466

页数：12

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