Hybrid Hydrogels Based on Polyethylene Glycol Bioconjugated with Silylated‑Amyloidogenic Peptides

Abstract

Hybrid-peptide hydrogel arrangements are a promising alternative to obtaining biocompatible structures at the nanoscopic scale. In this work, a new class of hybrid hydrogels was obtained through the sol-gel process based on the reaction between an amyloid-like octapeptide sequence [RF] 4 (where R = arginine and F = phenylalanine) covalently bonded with glycine-linked alkoxysilanes, and hybrid silylated polyethylene glycol (PEG). 1 H nuclear magnetic resonance (NMR), liquid chromatography-mass spectrometry (LC-MS), and Fourier transform infrared spectroscopy (FTIR) analyses were used, resulting in synthesized precursor/intermediate molecules. The structure of hybrid hydrogel fibers was studied by atomic force microscopy (AFM) and small-angle X-ray scattering (SAXS), where the existence of two regions in the Guinier plot was observed, one being predominantly formed by polymer while the other one by peptide chains. The rheological measurements showed that viscoelastic parameters depend on both the amount of silane peptide in the hydrogel matrix and increased temperature. Also, the FTIR spectra indicated the coexistence of antiparallel and parallel β-sheet structure patterns into amyloid fibril hydrogels, which can be modulated by peptide-silane coupling in each formulation. The analyzed hydrogels showed thixotropic and shear-thinning rheology at physiological pH, leaving open the opportunity to topical drug delivery system applications in the future.

Nanostructure Formation and Cell Spheroid Morphogenesis of a Peptide Supramolecular Hydrogel

“…The decameric peptide NH 2 -DGRL 4 DGW-COOH (D: aspartic acid, G: glycine, R: arginine, W: tryptophan, and L: leucine) was synthesized using standard solid-phase approaches via an Fmoc strategy using Wang resin as described elsewhere. 21 Briefly, the Fmoc-Trp-Wang resin was hydrated with dichloromethane for 15 min and two cycles of basic hydrolysis were performed with 4-methylpiperidine in DMF (20%, 10 mL, 15 min) to remove the Fmoc-protecting group. Coupling reactions were carried out with 2.50 equiv amino acid and 5.00 equiv DIC and HOBt in NMP (10 mL) for 4 and 12 h (G/W/L/ D and R, respectively).…”

“…Then, ice-cold diethyl ether was added to precipitate the peptide, which was successively washed with ice-cold diethyl ether and then lyophilized. 21 The yield was estimated at 40− 50%. The decameric peptide was characterized by liquid chromatography coupled to mass spectroscopy (LC−MS), Figure S1, revealing that about 86% of the product was composed of DGWL 4 RGD (measured Mw = 1158, calculated Mw = 1157.3).…”

“…The reaction was left under agitation for 4 h and the supernatant was collected by vacuum filtration. Then, ice-cold diethyl ether was added to precipitate the peptide, which was successively washed with ice-cold diethyl ether and then lyophilized . The yield was estimated at 40–50%.…”

Silylated biomolecules: Versatile components for bioinks

“…Recently, Alves et al reported silylated PEG hydrogels functionalized with an amyloid-like peptide. ( Decandio et al, 2020 ). Their preparation protocol included the use of DMSO, high concentration of sodium fluoride and refrigeration which is not compatible with cell encapsulation.…”

“…Alves and co-workers reported a silylated amyloid-like peptide for the preparation of amyloid fibril hydrogels. ( Decandio et al, 2020 ). The peptide was silylated with ICPTES on solid support before cleavage with TFA in the presence of water.…”