Self-Assembly Dipeptide Hydrogel: The Structures and Properties.

Liangchun Li,Li Xie,Rongqin Sun,Renlin Zheng

doi:10.3389/fchem.2021.739791

Liangchun Li, Li Xie + Show 2 more

Open Access

https://doi.org/10.3389/fchem.2021.739791

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Abstract

Self-assembly peptide-based hydrogels are well known and popular in biomedical applications due to the fact that they are readily controllable and have biocompatibility properties. A dipeptide is the shortest self-assembling motif of peptides. Due to its small size and simple synthesis method, dipeptide can provide a simple and easy-to-use method to study the mechanism of peptides’ self-assembly. This review describes the design and structures of self-assembly linear dipeptide hydrogels. The strategies for preparing the new generation of linear dipeptide hydrogels can be divided into three categories based on the modification site of dipeptide: 1) COOH-terminal and N-terminal modified dipeptide, 2) C-terminal modified dipeptide, and 3) uncapped dipeptide. With a deeper understanding of the relationship between the structures and properties of dipeptides, we believe that dipeptide hydrogels have great potential application in preparing minimal biocompatible materials.

Highlights

Hydrogels are cross-linked by three-dimensional networks of modified molecules that hold a large amount of water, which were first reported by Wichterle and Lím (1960)
2014), Fmoc-Tyr-Thr (Hughes et al, 2012, 2013), Fmoc-Tyr-Asn (Hughes et al, 2013), and Fmoc-Gly-Ser, which selfassembled into fibrillar structures like Fmoc-Phe-Phe, the results indicated that the π–π and hydrophobic interactions of intermolecular Fmoc groups are the main driving forces in the self-assembly process of these systems
For the uncapped dipeptide composed of natural amino acids, Ventura and coworkers have reported that Ile-Phe dipeptide can form a stable hydrogel at pH 5.8; later, Marchesan et al found out that Leu-Phe dipeptide could form a stable hydrogel in phosphate buffer (Bellotto et al, 2020)

Summary

INTRODUCTION

Hydrogels are cross-linked by three-dimensional networks of modified molecules that hold a large amount of water, which were first reported by Wichterle and Lím (1960). Adams and coworkers have demonstrated that the gradual removal of the charge allows lateral assembly of the molecules to form fibrous structures by π–π stacking and β-sheet formation (Chen et al, 2010a) They have found out that the nitrile or bromo groups substituted Nap-modified dipeptide have shown better hydrogelation properties than nonsubstituted ones, suggesting that the electron-withdrawing nature of the bromo and nitro groups, which reduced the electron density of the π-system, has an impact on the selfassembly properties of the dipeptides via aromatic stacking interactions. Ikeda et al have reported C-terminal hydrazide-modified dipeptide, Cbz-Phe-Phe-NHNH2, which showed limited aqueous solubility and could not form a hydrogel, but its carbohydrate derivatives could form a hydrogel (Tsuzuki et al, 2017) (Figure 9) They have found out that the disaccharide structures (epimer or glycosidic-bond geometry) have a significant effect on the formation ability of the hydrogel and the morphology of the self-assembled structures. Coutsolelos et al have synthesized several aliphatic dipeptides bearing various protecting groups and found out that Fmoc-IleIle-TPP (TPP: tetraphenyl porphyrin) formed a hydrogel in HFIP–water (2:8) solvent mixture, whereas TPP-Ile-Ile-OMe and Boc-Ile-Ile-TPP failed to form hydrogel due to the spherical assemblies in solvents (Figure 10) (Nikoloudakis et al, 2019)

UNCAPPED DIPEPTIDE

CONCLUSION