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

• Published in: Nano letters 2019-03, Vol.19 (3), p.1560-1569
• Main Authors: 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
• Format: Article
• Language: English
• ISSN: 1530-6984; 1530-6992
• DOI: 10.1021/acs.nanolett.8b04406

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 (K D = 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 biofunctional proteins.