期刊
NANO LETTERS
卷 19, 期 3, 页码 1560-1569出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.8b04406
关键词
Peptide folding; growth factor; biomimetics; self-assembly; IGF-1
类别
资金
- National Science Fund for Distinguished Young Scholars [31825012]
- National Key Research and Development Program of China [2017YFC1103502]
- NSFC [21875116, 51773097, 81830060, 81701840, 81772000, 31771066]
- National Program for Support of Top-notch Young Professionals
- Fundamental Research Funds for the Central Universities
- Young Elite Scientists Sponsorship Program by Tianjin [TJSQNTJ-2017-16]
- China Postdoctoral Science Foundation [2016M600185]
- Tianjin Science Fund for Distinguished Young Scholars [17JCJQJC44900]
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.
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