Supramolecular Nanofibers with Superior Bioactivity to Insulin-Like Growth Factor-I

Shang Yuna; Zhi Dengke; Feng Guowei; Wang Zhongyan; Mao Duo; Guo Shuang; Liu Ruihua; Liu Lulu; Zhang Shuhao; Sun Shenghuan; Wang Kai; Kong Deling; Gao Jie; Yang Zhimou

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Supramolecular Nanofibers with Superior Bioactivity to Insulin-Like Growth Factor-I

机译：超分子纳米纤维，具有优异的生物活性与胰岛素样生长因子-1

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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.

机译：衍生自蛋白质的生物活性肽通常需要折叠成二次结构以激活下游信号通路。然而，合成肽通常形成随机线圈，从而失去它们的生物活性。在这里，我们表明，通过引入自组装肽基序和使用不同的制剂途径，可以将来自胰岛素样生长因子-1（IGF-1）的肽折叠成α-螺旋和β-片。 β-片材对IGF-1受体（IGF-1R，11.5nm）表现出低离解常数，其仅比IGF-1（4.3nm）高出3倍。然而，没有自组装的α-螺旋螺旋形和肽显示IGF-1R（K-D = 179.1和321.6nm）的弱亲和力。在10nm下，β-薄片有效地激活IGF-1下游途径，显着提高HUVEC增殖和预防细胞凋亡。 β-片状肽显示出在体内IGF-1的优异性能，通过显着降低肌肉降低和增强肢体血管化来改善缺血性后肢挽损。我们的研究提供了一种有用的策略来限制肽变为不同构象，这可能导致模拟生物官能蛋白的超分子纳米材料的发育。

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来源
《Nano letters》 |2019年第3期|共10页
作者
Shang Yuna; Zhi Dengke; Feng Guowei; Wang Zhongyan; Mao Duo; Guo Shuang; Liu Ruihua; Liu Lulu; Zhang Shuhao; Sun Shenghuan; Wang Kai; Kong Deling; Gao Jie; Yang Zhimou;
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作者单位

Nankai Univ Collaborat Innovat Ctr Chem Sci &

Engn State Key Lab Med Chem Biol Key Lab Bioact Mat Minist Educ Coll Life Sci Tianjin 300071 Peoples R China;

Nankai Univ Collaborat Innovat Ctr Chem Sci &

Engn State Key Lab Med Chem Biol Key Lab Bioact Mat Minist Educ Coll Life Sci Tianjin 300071 Peoples R China;

Tianjin Med Univ Canc Inst &

Hosp Tianjin Key Lab Canc Prevent &

Therapy Tianjins Clin Res Ctr Canc Dept Genitourinary Oncol Natl Clin Res Ctr Canc Tianjin 300060 Peoples R China;

Nankai Univ Collaborat Innovat Ctr Chem Sci &

Engn State Key Lab Med Chem Biol Key Lab Bioact Mat Minist Educ Coll Life Sci Tianjin 300071 Peoples R China;

Natl Univ Singapore Dept Chem &

Biomol Engn Engn Dr 4 Singapore 117585 Singapore;

Nankai Univ Collaborat Innovat Ctr Chem Sci &

Engn State Key Lab Med Chem Biol Key Lab Bioact Mat Minist Educ Coll Life Sci Tianjin 300071 Peoples R China;

Nankai Univ Collaborat Innovat Ctr Chem Sci &

Engn State Key Lab Med Chem Biol Key Lab Bioact Mat Minist Educ Coll Life Sci Tianjin 300071 Peoples R China;

Nankai Univ Collaborat Innovat Ctr Chem Sci &

Engn State Key Lab Med Chem Biol Key Lab Bioact Mat Minist Educ Coll Life Sci Tianjin 300071 Peoples R China;

Nankai Univ Collaborat Innovat Ctr Chem Sci &

Engn State Key Lab Med Chem Biol Key Lab Bioact Mat Minist Educ Coll Life Sci Tianjin 300071 Peoples R China;

Nankai Univ Collaborat Innovat Ctr Chem Sci &

Engn State Key Lab Med Chem Biol Key Lab Bioact Mat Minist Educ Coll Life Sci Tianjin 300071 Peoples R China;

Nankai Univ Collaborat Innovat Ctr Chem Sci &

Engn State Key Lab Med Chem Biol Key Lab Bioact Mat Minist Educ Coll Life Sci Tianjin 300071 Peoples R China;

Nankai Univ Collaborat Innovat Ctr Chem Sci &

Engn State Key Lab Med Chem Biol Key Lab Bioact Mat Minist Educ Coll Life Sci Tianjin 300071 Peoples R China;

Nankai Univ Collaborat Innovat Ctr Chem Sci &

Engn State Key Lab Med Chem Biol Key Lab Bioact Mat Minist Educ Coll Life Sci Tianjin 300071 Peoples R China;

Nankai Univ Collaborat Innovat Ctr Chem Sci &

Engn State Key Lab Med Chem Biol Key Lab Bioact Mat Minist Educ Coll Life Sci Tianjin 300071 Peoples R China;

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原文格式 PDF
正文语种 eng
中图分类特种结构材料;物理化学（理论化学）、化学物理学;
关键词
Peptide folding; growth factor; biomimetics; self-assembly; IGF-1;

机译：肽折叠;生长因子;生物体;自组装;IGF-1;

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专利

1. Supramolecular Nanofibers with Superior Bioactivity to Insulin-Like Growth Factor-I [J] . Shang Yuna, Zhi Dengke, Feng Guowei, Nano letters . 2019,第3期

机译：超分子纳米纤维，具有优异的生物活性与胰岛素样生长因子-1
2. Proteolytic Conversion of Insulin-like Growth Factor-I to des (1-3) Insulin-like Growth Factor-I: A Further Site of Regulation of Insulin-like Growth Factor-I Action [J] . Liam J Murphy, Hiroyuki Yamamoto, Yang Lu Clinical Pediatric Endocrinology . 1996,第Supple8期

机译：胰岛素样生长因子-I的蛋白水解转化为des（1-3）胰岛素样生长因子-I：调节胰岛素样生长因子-I作用的另一个位点
3. Insulin-like growth factor-I and insulin-like growth factor binding protein-3 cotreatment versus insulin-like growth factor-I alone in two brothers with growth hormone insensitivity syndrome: Effects on insulin sensitivity, body composition and linear growth [J] . Ekstr?mK., Carlsson-SkwirutC., RitzénE.M., Hormone research in p?diatrics . 2011,第5期

机译：胰岛素样生长因子-I和胰岛素样生长因子结合蛋白-3的联合治疗与单独的胰岛素样生长因子-I在两个患有生长激素不敏感综合征的兄弟中的关系：对胰岛素敏感性，身体组成和线性生长的影响
4. Changes in the growth hormone/insulin-like growth factor-I axis during the early postnatal development of Tibet piglets (a typical mini pig) [C] . Q.Hu, M.J.Bo, P.Kang, Progress in functional amino acids and carbohydrates for animal production . 2009

机译：西藏仔猪（典型小型仔猪）出生后早期生长激素/胰岛素样生长因子-I轴的变化
5. Insulin-like growth factor-I in fibroproliferative acute respiratory distress syndrome: The molecular mechanisms of tumor necrosis factor regulated insulin-like growth factor-I production in macrophages. [D] . Krein, Peter M. 2003

机译：纤维增生性急性呼吸窘迫综合征中的胰岛素样生长因子-I：肿瘤坏死因子调节巨噬细胞中胰岛素样生长因子-I产生的分子机制。
6. Purified hybrid insulin/insulin-like growth factor-I receptors bind insulin-like growth factor-I but not insulin with high affinity. [O] . M A Soos, C E Field, K Siddle 1993

机译：纯化的杂合胰岛素/胰岛素样生长因子-I受体以高亲和力结合胰岛素样生长因子-I但不结合胰岛素。
7. Proteolytic Conversion of Insulin-like Growth Factor-I to des (1-3) Insulin-like Growth Factor-I: A Further Site of Regulation of Insulin-like Growth Factor-I Action [O] . Liam J Murphy, Hiroyuki Yamamoto, Yang Lu 1996

机译：胰岛素样生长因子-1的蛋白水解转化为DES（1-3）胰岛素样生长因子-1：进一步调节胰岛素样生长因子-I作用的调节部位

Supramolecular Nanofibers with Superior Bioactivity to Insulin-Like Growth Factor-I

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