Synthesis and characterization of mono S-lipidated peptide hydrogels: a platform for the preparation of reactive oxygen species responsive materials?

Organic & Biomolecular Chemistry Pub Date: 2021-03-25 DOI: 10.1039/D1OB00355K

Abstract

In this work we report the synthesis of mono lipidated peptides containing a 3-mercaptopropionate linker in the N-terminus by means of a photoinitiated thiol–ene reaction (S-lipidation). We evaluate the self-assembling and hydrogelation properties of a library of mono S-lipidated peptides containing lipid chains of various lengths and demonstrate that hydrogelation was driven by a balance between the lipid chain's hydrophobicity and the peptide's facial hydrophobicity. We further postulate that a simple calculation using estimated values of log?D could be used as a predictor of hydrogelation when designing similar systems. A mono S-lipidated peptide containing a short lipid chain that formed hydrogels was fully characterized and a mechanism for the peptide hydrogelation developed. Finally, we demonstrate that the presence of the thioether group in the mono S-lipidated peptide hydrogels, which is a feature lacking in conventional N-acyl lipidated systems, enables the controlled disassembly of the gel via oxidation to the sulfoxide by reactive oxygen species in accordance with a hydrophobicity-modulated strategy. Thus, we conclude that mono S-lipidated peptide hydrogels constitute a novel and simple tool for the development of tissue engineering and targeted drug delivery applications of diseases with overexpression of reactive oxygen species (e.g. degenerative and metabolic diseases, and cancers).

Graphical abstract: Synthesis and characterization of mono S-lipidated peptide hydrogels: a platform for the preparation of reactive oxygen species responsive materials
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