Enzyme Instructed Self‐assembly of Naphthalimide‐dipeptide: Spontaneous Transformation from Nanosphere to Nanotubular Structures that Induces Hydrogelation

Abstract

Understanding the structure‐morphology relationships of self‐assembled nanostructures is crucial for developing materials with the desired chemical and biological functions. Here, phosphate‐based naphthalimide (NI) derivatives have been developed for the first time to study the enzyme‐instructed self‐assembly process. Self‐assembly of simple amino acid derivative NI‐Yp resulted in non‐specific amorphous aggregates in the presence of alkaline phosphatase enzyme. On the other hand, NI‐FYp dipeptide forms spherical nanoparticles under aqueous conditions which slowly transformed into partially unzipped nanotubular structures during the enzymatic catalytic process through multiple stages which subsequently resulted in hydrogelation. The self‐assembly is driven by the formation of β‐sheet type structures stabilized by offset aromatic stacking of NI core and hydrogen bonding interactions which is confirmed with PXRD, Congo‐red staining and molecular mechanical calculations. We propose a mechanism for the self‐assembly process based on TEM and spectroscopic data. The nanotubular structures of NI‐FYp precursor exhibited higher cytotoxicity to human breast cancer cells and human cervical cancer cells when compared to the nanofiber structures of the similar Fmoc‐derivative. Overall this study provides a new understanding of the supramolecular self‐assembly of small‐molecular‐weight hydrogelators.

Nanotubes and water-channels from self-assembling dipeptides

“…The NTs formed a luminescent hydrogel. 97 Table 3 Heterochiral hydrophobic dipeptides forming NTs with waterfilled internal cavities (cyan cells) defined by 4 (D) or 6 (F) peptide molecules. [77][78][79] ''-'' means no data is available Fig.…”

Influence of metal ion crosslinking on the nanostructures, stiffness, and biofunctions of bioactive peptide hydrogels

“…A slight reflection at 4.5 Å is most likely due to the "cross-β" packing orientation. 45 Hydrogelator 1b showed similar spectral properties, while 1c with Ba 2+ exhibited crystal-like spectral properties, which could be due to a poor cleavage effect (Fig. S10d †).…”

Self-Assembly Dipeptide Hydrogel: The Structures and Properties

“…Furthermore, the NI-Tyr-Phe showed low cytotoxicity and could be applied as a suitable carrier for drug delivery. They have also developed NI-modified phosphate-based dipeptide NI-FY p ( Chakravarthy et al, 2020 ) ( Figure 3 ), which formed spherical nanoparticles in the aqueous condition firstly, and then in the condition of enzymatic catalysis, they slowly transformed into partially unzipped nanotubular structures and subsequently resulted in hydrogelation.…”

“… (A) The illustration of self-assembly NI-FY p dipeptide nanostructures which transformed from spherical nanoparticles into a hydrogel during the enzymatic catalytic process; (B) TEM image of NI-FY p nanoparticles in Tris-buffer (10 mM); (C) particle size distribution histogram of NI-FY p (10 mM) nanoparticles by TEM and DLS measurements; (D) TEM images of NI-FY p treated with 10 U of ALP ( Chakravarthy et al, 2020 ). …”