Background

The complement system is a key player in innate immunity and a modulator of the adaptive immune system. Among the three pathways of complement, the alternative pathway (AP) accounts for most of the complement activation. Factor B (FB) is a major protease of the AP, making it a promising target to inhibit the AP activity in conditions of uncontrolled complement activation.

Methods

Based on the data obtained from sequence analysis and conformational changes associated with FB, we expressed and purified a recombinant FB fragment (FBfr). We tested the inhibitory activity of the protein against the AP by in vitro assays.

Results

FBfr protein was proven to inhibit the complement AP activity when tested by C3b deposition assay and rabbit erythrocyte hemolytic assay.

Conclusion

Our recombinant FBfr was able to compete with the native human FB, which allowed it to inhibit the AP activity. This novel compound is a good candidate for further characterization and testing to be used in complement diagnostic tests and as a drug lead in the field of complement therapeutics.

中文翻译：

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B因子的小片段作为补体旁路活性的潜在抑制剂

背景

补体系统是先天免疫的关键参与者和适应性免疫系统的调节剂。在补体的三种途径中，替代途径（AP）占补体激活的大部分。因子 B (FB) 是 AP 的主要蛋白酶，使其成为在不受控制的补体激活条件下抑制 AP 活性的有希望的靶标。

方法

基于从序列分析获得的数据和与FB相关的构象变化，我们表达并纯化了重组FB片段（FBfr）。我们通过体外测定测试了蛋白质对 AP 的抑制活性。

结果

当通过 C3b 沉积试验和兔红细胞溶血试验测试时，FBfr 蛋白被证明可以抑制补体 AP 活性。

结论

我们的重组 FBfr 能够与天然人类 FB 竞争，这使其能够抑制 AP 活性。这种新型化合物是用于补体诊断测试和作为补体治疗领域药物先导的进一步表征和测试的良好候选者。