Novel Design of Peptides to Reverse the Anticoagulant Activities of Heparin and other Glycosaminoglycans

Novel Design of Peptides to Reverse the Anticoagulant Activities of Heparin and other Glycosaminoglycans
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逆转肝素和其他糖胺聚糖抗凝活性的肽的新颖设计

DOI:
10.1055/s-0037-1615609
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发表时间:
2001
影响因子:
6.7
通讯作者:
Josè Martinez
Josè Martinez
中科院分区:
医学2区
文献类型:
--
作者:
B. Schick;J. Gradowski;J. S. San Antonio;Josè Martinez

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使用未分离肝素、低分子量肝素或丹那帕肽进行抗凝治疗的患者可能会出现大量出血,需要逆转抗凝药物。鱼精蛋白是目前唯一可用于逆转未分离肝素的药物。鱼精蛋白对接受过低分子量肝素或那那帕肽治疗的患者无效。我们根据公认的肝素结合序列(Verrecchio et al., J Biol Chem 2000; 275: 7701-7707)开发了一系列肽,这些肽能够在体外中和未分离肝素的抗凝血酶活性,在体外中和未分离肝素、依诺肝素(Lovenox)和danaparoid (organan)的抗Xa因子活性,以及在大鼠体内中和依诺肝素的抗Xa因子活性。这些肽可作为鱼精蛋白逆转UFH的替代品,并可用于中和人体内的依诺肝素和丹那那肝素。
Summary Patients undergoing anticoagulation with unfractionated heparin, low molecular weight heparin, or danaparoid may experience excess bleeding which requires reversal of the anticoagulant agent. Protamine is at present the only agent available for reversal of unfractionated heparin. Protamine is not effective in patients who have received low molecular weight heparin or danaparoid. We have developed a series of peptides based on consensus heparin binding sequences (Verrecchio et al., J Biol Chem 2000; 275: 7701-7707) that are capable of neutralizing the anti-thrombin activity of unfractionated heparin in vitro, the antifactor Xa activity of unfractionated heparin, Enoxaparin (Lovenox) and danaparoid (Orgaran) in vitro and the anti-Factor Xa activity of Enoxaparin in vivo in rats. These peptides may serve as alternatives for Protamine reversal of UFH and may be useful for neutralization of enoxaparin and danaparoid in humans.
通过生物物理和生物测定以及肽-五糖对接复合物的分子模型评估抗凝血酶 III-肝素相互作用的结构-功能关系。
DOI: 10.1006/abbi.1996.0448
发表时间: 1996
期刊: Archives of biochemistry and biophysics.
影响因子: --
作者:
Tyler-Cross,R;Sobel,M;McAdory,LE;Harris,RB
通讯作者: Harris,RB
依诺肝素抑制狒狒体外循环期间凝血酶的形成和活性。
DOI: 10.1016/s0022-5223(98)70057-1
发表时间: 1998
期刊: The Journal of thoracic and cardiovascular surgery
影响因子: --
作者:
Gikakis,N;Rao,AK;Miyamoto,S;Gorman3rd,JH;Khan,MM;Anderson,HL;Hack,CE;Sun,L;Niewiarowski,S;Colman,RW;EdmundsJr,LH
通讯作者: EdmundsJr,LH