Supramolecular Nanofibers with Superior Bioactivity to Insulin-Like Growth Factor-I
Supramolecular Nanofibers with Superior Bioactivity to Insulin-Like Growth Factor-I
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具有优于胰岛素样生长因子 I 的生物活性的超分子纳米纤维
DOI：
10.1021/acs.nanolett.8b04406
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发表时间：
2019-03-01
期刊：
影响因子：
10.8
通讯作者：
Yang, Zhimou
中科院分区：
文献类型：
--
作者：
Shang, Yuna;Zhi, Dengke;Yang, Zhimou
衍生自蛋白质的生物活性肽通常需要折叠成二级结构以激活下游信号传导途径。然而，合成肽通常形成无规卷曲，从而失去其生物活性。在这里，我们表明，通过引入自组装肽基序和使用不同的制备途径，胰岛素样生长因子-I（IGF-1）的肽可以折叠成α-螺旋和β-折叠。β折叠蛋白对IGF-1受体（IGF-1 R，11.5 nM）的解离常数较低，仅为IGF-1（4.3 nM）的3倍。然而，α-螺旋肽和没有自组装基序的肽显示出对IGF-1 R的弱亲和力（K-D分别为179.1和321.6 nM）。在10 nM时，β-折叠蛋白有效激活IGF-1下游通路，显著增强HUVEC增殖并防止细胞凋亡。β折叠肽在体内表现出上级IGF-1的性能，并且通过显著减少肌肉降解和增强肢体血管化来改善缺血性后肢挽救。我们的研究提供了一个有用的策略，以限制肽到不同的构象，这可能会导致模仿生物功能蛋白质的超分子纳米材料的发展。
Bioactive peptides derived from proteins generally need to be folded into secondary structures to activate downstream signaling pathways. However, synthetic peptides typically form random-coils, thus losing their bioactivities. Here, we show that by introducing a self-assembling peptide motif and using different preparation pathways, a peptide from insulin-like growth factor-I (IGF-1) can be folded into an alpha-helix and beta-sheet. The beta-sheet one exhibits a low dissociation constant to the IGF-1 receptor (IGF-1R, 11.5 nM), which is only about 3 times higher than that of IGF-1 (4.3 nM). However, the alpha-helical one and the peptide without self-assembling motif show weak affinities to IGF-1R (K-D = 179.1 and 321.6 nM, respectively). At 10 nM, the beta-sheet one efficiently activates the IGF-1 downstream pathway, significantly enhancing HUVEC proliferation and preventing cell apoptosis. The beta-sheet peptide shows superior performance to IGF-1 in vivo, and it improves ischemic hind-limb salvage by significantly reducing muscle degradation and enhancing limb vascularization. Our study provides a useful strategy to constrain peptides into different conformations, which may lead to the development of supramolecular nanomaterials mimicking biofunctional proteins.