Sequence Adaptive Peptide–Polysaccharide Nanostructures by Biocatalytic Self-Assembly

Abstract

Co-assembly of peptides and polysaccharides can give rise to formation of nanostructures with tunable morphologies. We show that in situ enzymatic exchange of a dipeptide sequences in aromatic peptide amphiphiles/polysaccharide co-assemblies enables dynamic formation and degradation of different nanostructures depending on the nature of the polysaccharide present. This is achieved in a one-pot system composed of Fmoc-cystic acid (CA), Fmoc-lysine (K) plus phenylalanine amide (F) in the presence of thermolysin which, through dynamic hydrolysis and amide formation gives rise to dynamic peptide library composed of the corresponding Fmocdipeptides (CAF and KF). When the cationic polysaccharide chitosan is added to this mixture, selective amplification of the CAF peptide is observed giving rise to formation of nanosheets through co-assembly. By contrast, upon addition of anionic heparin, KF is formed which gives rise to a nanotube morphology. The dynamic adaptive potential was demonstrated by sequential morphology changes depending on the sequence of polysaccharide addition. This first demonstration of the ability to access different peptide sequences and nanostructures depending on presence of biopolymers may pave the way to biomaterials that can adapt their structure and function and may be of relevance in design of materials able to undergo dynamic morphogenesis.

Two‐Step Assembly of Thermoresponsive Gold Nanorods Coated with a Single Kind of Ligand

“…This multistep bottom-up approach and reversible assembly/disassembly are crucial concepts for fabrication of the sophisticated hierarchical structures. [9,10] To realize reversible multistep assembly, the design of the primary structure is important.…”

“…Additionally, the assembly and disassembly of the tertiary structures to form the quaternary structure occur reversibly in response to environmental changes that induce dynamic functions. This multistep bottom‐up approach and reversible assembly/disassembly are crucial concepts for fabrication of the sophisticated hierarchical structures . To realize reversible multistep assembly, the design of the primary structure is important.…”

Exploring Strategies To Bias Sequence in Natural and Synthetic Oligomers and Polymers

“…5 Natural polymers as templates for sequence specific polymerization Sequence controlled polymerization in natural polymers such as proteins is perfectly controlled by template-(macro)molecules bearing sequence information through which monomers can be selectively recognized and coupled. Inspired by that, natural templateassisted constrained peptide sequence synthesis and selection was recently achieved for an enzymatically catalyzed mixture utilizing electrostatic interactions between charged amino acids and oppositely charged polysaccharide templates 6 . In the absence of any template, peptide sequence selection could be also achieved under programmable reaction conditions.…”

Molecular Self‐Assembly Constructed in Physiological Conditions for Cancer Diagnosis and Therapy

“…This can be explained by the fact that the self‐assembling process of the Fmoc‐FF‐NH 2 was directed by the stacking interactions, which were altered by the electronic substituent groups. Besides, the addition of polysaccharides to co‐assemble with peptides would lead to the formation of tunable supramolecular structures according to the properties of polysaccharides . Two Fmoc‐protected amino acids (Fmoc‐cysteic acid [CA], Fmoc‐lysine [K]) were mixed with phenylalanine amide and thermolysin to generate a dynamic dipeptide library (CAF and KF) through the enzyme‐triggered condensation reaction.…”