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

Nano Letters
Yuna ShangZhimou Yang

Abstract

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 α-helix and β-sheet. The β-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 α-helical one and the peptide without self-assembling motif show weak affinities to IGF-1R ( KD = 179.1 and 321.6 nM, respectively). At 10 nM, the β-sheet one efficiently activates the IGF-1 downstream pathway, significantly enhancing HUVEC proliferation and preventing cell apoptosis. The β-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 biofu...Continue Reading

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Citations

Apr 12, 2019·Chemical Communications : Chem Comm·Yuna ShangZhimou Yang
Jan 9, 2020·Nanoscale·Xinxin LiZhimou Yang
Dec 29, 2020·International Journal of Nanomedicine·Chaoshan HanJunjie Yang
Jan 1, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Sheng ZengDan Ding
Nov 2, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Masoud FarshbafPaul R Walker
Aug 20, 2020·Chemical Reviews·Hongjian HeBing Xu
May 21, 2021·Advanced Drug Delivery Reviews·Zhenghao ZhangXingyi Li
Aug 12, 2019·ACS Biomaterials Science & Engineering·Zhaozhao DingDavid L Kaplan
Sep 30, 2020·Langmuir : the ACS Journal of Surfaces and Colloids·Harsimran KaurSangita Roy
Dec 9, 2019·ACS Biomaterials Science & Engineering·Pooja SharmaSangita Roy
May 1, 2020·ACS Applied Materials & Interfaces·Chunhui LiangJie Gao
Dec 24, 2019·Langmuir : the ACS Journal of Surfaces and Colloids·Vijay Kumar PalSangita Roy

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