摘要
目的:研究基因重组的新型多肽bg115-2体外对活化凝血因子Ⅹ(FⅩa)的抑制作用、与酶结合的动力学特点及抗凝血活性。方法:用发色底物法测定bg115-2的FⅩa抑制活性、特点和酶结合性质;用活化的部分凝血活酶时间(APTT)和凝血酶原时间(PT)试剂盒测定bg115-2对于大鼠血浆凝血时间的影响。结果:bg115-2具有浓度依赖的FⅩa抑制活性,IC50为13.1×10-9mol.L-1,Ki为7.3×10-9mol.L-1;bg115-2对FⅩa的抑制活性随时间延长而增强;稀释反应混合物未使FⅩa的活性恢复;bg115-2可浓度依赖性延长APTT及PT,使APTT延长1倍的浓度为1.3×10-7mol.L-1,使PT延长1倍的浓度为3.0×10-7mol.L-1。结论:bg115-2为一强活性的、慢结合的、不可逆的FⅩa抑制剂,具有较强的抗凝血活性。
Objective： To study the in vitro F X a inhibitory effect, the enzyme-binding kinetics and anticoagulating activity of bg115-2, a novel peptide designed and expressed recently. Methods： Chromogenic-substrate method was used to assess the inhibitory effect on FXa and the binding kinetics of bg115-2, and commercial kits of activated partial thromboplastin time （APTT） and prothrombin time （PT） were used to test its anti-coagulative ac- tivity. Results： bg115-2 potently and concentration-dependently inhibited F X a activity with an IC50 of 13.1 ×10^-9 mol· L^-1 and a Ki of 7. 3 × 10^-9 mol· L^-1 , and the inhibition was increased with the prolongation of incubation time. The dilution of reaction mixtures did not recover the F X a activity from the inhibition by bg115-2. In addition, bg115-2 prolonged APTT and PT of rat plasma in a concentration-dependent manner; the concentrations required for doubling APTT and PT were 1.3× 10^-7 mol·L^-1 and 3.0 × 10^-7 mol· L^-1, respectively. Conclusion： bg115-2, a novel peptide, is a potent, slow-binding and irreversible F X a inhibitor with stronger anti-coagulating effect.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2008年第8期656-660,共5页
Chinese Journal of New Drugs
