Short self‐assembling peptides with a urea bond: A new type of supramolecular peptide hydrogel materials

Abstract

There is an increasing need to develop short self-assembling peptides (SAPs) that can form hydrogels for cell engineering and biomedical applications. In this study, we proposed new short self-assembling peptides with a symmetric structure via a urea bond. (FFiO) 2 and (FFiK) 2 were designed as amphiphilic peptides with a hydrophobic domain inside of zwitterionic hydrophilic ends and a urea bond embedded in the hydrophobic domain. The two peptides were synthesized by a liquid-phase method. The simple structural design of these peptides makes their synthesis on a large scale possible. Both (FFiO) 2 and (FFiK) 2 assembled into β-sheet structure and formed stable hydrogels under physiological pH conditions in a pH-responsive manner. The urea bond was important for the formation of transparent hydrogels. Since (FFiK) 2 exhibited self-assembling properties superior to those of (FFiO) 2 , (FFiK) 2 hydrogels were used as scaffolds for cell culture. (FFiK) 2 hydrogels supported cell proliferation without significant cytotoxicity. Therefore, (FFiK) 2 is a beneficial supramolecular peptide hydrogelator for cell engineering.

Recent Advances in Zwitterionic Hydrogels: Preparation, Property, and Biomedical Application

“…Phenylalanine peptide and its derivatives are suitable for self-assembly prepared transparent hydrogel due to a strong π-π stacking on aromatic groups [ 40 , 41 ]. Tsutsumi et al [ 42 ] further introduced a urea bond to form a strong hydrogen bond network to stabilize the self-assembly structure ( Figure 4 c). There are no potential toxic small molecules retained during hydrogel formation in this approach, which is suitable for the clean environment required application [ 42 , 43 ].…”

“…Tsutsumi et al [ 42 ] further introduced a urea bond to form a strong hydrogen bond network to stabilize the self-assembly structure ( Figure 4 c). There are no potential toxic small molecules retained during hydrogel formation in this approach, which is suitable for the clean environment required application [ 42 , 43 ].…”

“…( c ) Self-assembly using urea bond to form a strong hydrogen bond network. Reproduced with permission from [ 42 ]. Copyright 2020 Wiley Periodicals LLC.…”

Peptide-Based Low Molecular Weight Photosensitive Supramolecular Gelators

“…Though the individual supramolecular interactions are weak, the resultant interaction is strong enough to make soft materials with different nanostructures, functions, and elegant properties when they work in tandem. An extreme case of higher order self-assembly is the formation of supramolecular gels, basically, semi-solid materials composed of three-dimensional (3D) networked structures with a large amount of entrapped solvents (water in the case of hydrogels and other solvents for organogels) [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Due to the reversible nature of the supramolecular interactions, such as hydrogen bonding, π−π stacking, hydrophobic interactions, van der Waals interactions, charge-transfer interactions, etc., the resultant gels are highly sensitive to different external stimuli and thus making those gels highly dynamic in nature [ 14 , 15 , 16 ].…”

Fatty Acids/Tetraphenylethylene Conjugates: Hybrid AIEgens for the Preparation of Peptide-Based Supramolecular Gels

“…In particular, the obtained compounds were used as N- terminus capping agents in the development of peptide-based materials. Peptides are indeed able to organize themselves into ordered structures and are widely exploited in the development of smart materials ( Clerici et al, 2016 ; Fuertes et al, 2017 ; Gagni et al, 2019 ; Banerjee and Hamley, 2020 ; Locarno et al, 2020 ; Vaghi et al, 2020 ; Varanko et al, 2020 ; Bucci et al, 2021a ; Bucci et al, 2021b ; Surís-Valls et al, 2022 ) and supramolecular gels ( Makam and Gazit, 2018 ; Jain and Roy, 2020 ; Tsutsumi et al, 2021 ; Kurbasic et al, 2022 ). Ultra-short peptides derived from natural proteins, such as amyloidogenic ones, have been investigated, the phenylalanine dipeptide being the most exploited motif ( Diaferia et al, 2019 ; Bucci et al, 2020 ; Gil et al, 2020 ; Ji et al, 2021 ; Criado-Gonzalez et al, 2022 ).…”