Novel complementary peptides to target molecules.
Novel complementary peptides to target molecules.
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发表时间：
2011-07
影响因子：
2
通讯作者：
H. Okada;M. Imai;F. Ono;Alan Okada;T. Tada;Y. Mizue;K. Terao;N. Okada
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文献类型：
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作者：
H. Okada;M. Imai;F. Ono;Alan Okada;T. Tada;Y. Mizue;K. Terao;N. Okada
我们生成了一个进化的计算机程序，该程序生成互补肽（C-pep）序列，通过比较每对互补肽的几个物理化学参数，具有与靶肽相互作用的潜力。我们生成了C-peps来靶向几种分子。约30%的合成C-peps干扰其靶点的功能。C5 a刺激TNFα和其他炎性细胞因子的产生。C5 a的抑制应该对脓毒症有效，脓毒症损害了癌症患者的状态。C5 a的抑制性C-pep之一，称为AcPepA，在静脉输注致死剂量的细菌LPS（4 mg/kg）的食蟹猴中有效，注定会死亡。通过静脉内施用2 mg/kg/h的AcPepA来拯救猴。AcPepA的优异治疗效果可能是由于限制了由C5 a对C5 L2（其为第二C5 a受体）的作用诱导的高迁移率族蛋白1（HMGB 1）激增，因为释放的HMGB 1具有刺激作为内源性配体的TLR 4的能力，导致进一步活化炎性细胞以释放炎性细胞因子，形成炎症的正反馈回路。
We generated an evolutionary computer program that generates complementary peptide (C-pep) sequences, with the potential to interact with a target peptide, by comparing several physico-chemical parameters of each pair of the complementary peptides being analyzed. We generated C-peps to target several molecules. About 30% of synthesized C-peps interfered with the function of their targets. C5a stimulates generation of TNFα and other inflammatory cytokines. Inhibition of C5a should be effective against sepsis, which impairs the status of cancer-bearing patients. One of the inhibitory C-peps of C5a, termed AcPepA, was effective in Cynomolgus monkeys intravenously infused with a lethal dose of bacterial LPS (4 mg/kg) destined to die. The monkeys were rescued by intravenous administration of 2 mg/kg/h of AcPepA. The excellent therapeutic effect of AcPepA is likely to be due to restriction of high mobility group box 1 (HMGB1) surge induced by the effect of C5a on C5L2, which is the second C5a receptor, since the released HMGB1 has the capacity to stimulate TLR4 as an endogeneous ligand resulting in further activation of inflammatory cells to release inflammatory cytokines forming a positive feedback circuit of inflammation.