Heparin mapping using heparin lyases and the generation of a novel low molecular weight heparin.
Heparin mapping using heparin lyases and the generation of a novel low molecular weight heparin.
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DOI：
10.1021/jm101381k
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发表时间：
2011-01-27
影响因子：
7.3
通讯作者：
Linhardt RJ
中科院分区：
文献类型：
--
作者：
Xiao Z;Tappen BR;Ly M;Zhao W;Canova LP;Guan H;Linhardt RJ
用肝素裂解酶1、2或3酶切7种药物肝素，然后用高效液相色谱分析，对7种药物肝素进行寡糖图谱分析。首次报道了利用肝素裂解酶2或肝素裂解酶3从连接区释放的一种作图标准ΔUA-Gal-Gal-Xyl-O-CH2CONHCHCOOH(其中ΔUA是4-脱氧-α-L-苏糖-十六烷-4-烯-吡喃糖醛酸，Gal是β-D-半乳糖，而XYL是β-D-木糖)。肝素裂解酶3裂解位点的敏感性也呈大小依赖性。肝素裂解酶3作用于肝素链的硫酸盐化程度较低的区域，并不切断肝素的抗凝血酶III结合部位内的连接。因此，基于这种独特的底物特异性，一种新型的低分子肝素(LMWH)被提供给肝素裂解酶3消化肝素，它具有与现有LMWH相当的抗凝血活性。
Seven pharmaceutical heparins were investigated by oligosaccharide mapping by digestion with heparin lyase 1, 2 or 3, followed by high performance liquid chromatography analysis. The structure of one of the prepared mapping standards, ΔUA-Gal-Gal-Xyl-O-CH2CONHCH2COOH, (where ΔUA is 4-deoxy-α-L-threo-hex-4-eno-pyranosyluronic acid, Gal is β-D-galactpyranose, and Xyl is β-D-xylopyranose) released from the linkage region using either heparin lyase 2 or heparin lyase 3 digestion, is reported for the first time. A size-dependent susceptibility of site cleaved by heparin lyase 3 was also observed. Heparin lyase 3 acts on the under sulfated domains of the heparin chain and does not cleave the linkages within heparin’s antithrombin III binding site. Thus, a novel low molecular weight heparin (LMWH) was afforded on heparin lyase 3 digestion of heparin due to this unique substrate specificity, which has anticoagulant activity comparable to that of currently available LMWH.
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影响因子：
3.8
作者：
EDENS, RE;ALHAKIM, A;LINHARDT, RJ
通讯作者：
LINHARDT, RJ
影响因子：
7.4
作者：
Korir, Albert K.;Lirntiaco, John F. K.;Larive, Cynthia K.
通讯作者：
Larive, Cynthia K.
影响因子：
2.9
作者：
Laremore TN;Ly M;Solakyildirim K;Zagorevski DV;Linhardt RJ
通讯作者：
Linhardt RJ
影响因子：
4.3
作者：
JANDIK, KA;GU, KA;LINHARDT, RJ
通讯作者：
LINHARDT, RJ
DOI：
10.1006/bbrc.1996.1246
发表时间：
1996-08-23
影响因子：
3.1
作者：
Godavarti, R;Davis, M;Sasisekharan, R
通讯作者：
Sasisekharan, R