Supramolecular Nanofibers with Superior Bioactivity to Insulin-Like Growth Factor-I.
Nano Lett
; 19(3): 1560-1569, 2019 03 13.
Article
en En
| MEDLINE
| ID: mdl-30789273
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 ß-sheet. The ß-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 ß-sheet one efficiently activates the IGF-1 downstream pathway, significantly enhancing HUVEC proliferation and preventing cell apoptosis. The ß-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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
/
Factor I del Crecimiento Similar a la Insulina
/
Receptor IGF Tipo 1
/
Nanofibras
Límite:
Humans
Idioma:
En
Revista:
Nano Lett
Año:
2019
Tipo del documento:
Article