Unusual Two‐Step Assembly of a Minimalistic Dipeptide‐Based Functional Hypergelator

Abstract

Self‐assembled peptide hydrogels represent the realization of peptide nanotechnology into biomedical products. There is a continuous quest to identify the simplest building blocks and optimize their critical gelation concentration (CGC). Herein, a minimalistic, de novo dipeptide, Fmoc‐Lys(Fmoc)‐Asp, as an hydrogelator with the lowest CGC ever reported, almost fourfold lower as compared to that of a large hexadecapeptide previously described, is reported. The dipeptide self‐assembles through an unusual and unprecedented two‐step process as elucidated by solid‐state NMR and molecular dynamics simulation. The hydrogel is cytocompatible and supports 2D/3D cell growth. Conductive composite gels composed of Fmoc‐Lys(Fmoc)‐Asp and a conductive polymer exhibit excellent DNA binding. Fmoc‐Lys(Fmoc)‐Asp exhibits the lowest CGC and highest mechanical properties when compared to a library of dipeptide analogues, thus validating the uniqueness of the molecular design which confers useful properties for various potential applications.

Co‐Assembly between Fmoc Diphenylalanine and Diphenylalanine within a 3D Fibrous Viscous Network Confers Atypical Curvature and Branching

“…The formation of hydrogel‐like aggregate is a result of the delicate balance between these stacking patterns. This assembly mechanism is different from that of Fmoc‐based hydrogel we studied before, [31, 47] where Fmoc rings are responsible for both the formation of scaffolds and branching of the hydrogels.…”

Co‐Assembly between Fmoc Diphenylalanine and Diphenylalanine within a 3D Fibrous Viscous Network Confers Atypical Curvature and Branching

“…Thea ddition of FmocFF stock solutions to the FF solution immediately generated turbidity in the preparations which then rapidly turned transparent, characteristic of shortpeptide gelation. [31] Indeed, transmission electron microscopy (TEM) confirmed the presence of fibers ( Figure S2). After ac ertain time,t he microcrystalline structures started to appear.…”

“…Each composite system is denoted hereafter as FF/FmocFF( x ), where x is the concentration of FmocFF in wt %. The addition of FmocFF stock solutions to the FF solution immediately generated turbidity in the preparations which then rapidly turned transparent, characteristic of short‐peptide gelation [31] . Indeed, transmission electron microscopy (TEM) confirmed the presence of fibers (Figure S2).…”

Recent Progress in the Design and Application of Supramolecular Peptide Hydrogels in Cancer Therapy

“…[71] Very recently, a novel aromatic dipeptide (Fmoc-Lys(Fmoc)-Asp) was reported by Gazit and coworkers. [72] Due to the strong intramolecular and intermolecular aromatic interaction, the reported molecule had an ultra-low critical gelation concentration (0.002 wt%, 28.3 × 10 −6 m). More importantly, it showed a novel two-step assembly process, starting from spherebased opaque hydrogel to filament-based transparent hydrogel.…”