Supramolecular Assembly of a Molecularly Engineered Protein and Polymer

Abstract

Programmable assembly of biomolecules is af ast growing research area that aims to emulate nature's elegance in creating numerous hierarchicals elf-assembled structures, which are responsible for unimaginably difficult biological functions. Protein assembly is ap articularly challenging task, owing to their structural diversity,c onformational heterogeneity,a nd high molecular weight. This article reveals the ability of as upramoleculars tructure-directing unit (SSDU) to regulate the entropically favourable supramolecular assembly of ac ovalently conjugated protein (bovine serum albumin (BSA)) to produce well-defined protein-decorated micelles with remarkably high thermal stability,s uppression of the thermald enaturation of the protein, and retention of enzymatic activity.F urthermore, aS SDU-appendedt hermo-responsive poly(N-isopropylacrylamide) (PNIPAM) co-assembles with the SSDU-BSA conjugate because,i nb oth cases, assembly was primarily driven by specific molecular recognition between the SSDUs. However, the resulting supramolecular protein-polymer conjugate exhibits distinctly different polymersome structure to that of the micellar particle produced by the protein-SSDUc onjugate. In this case, the enzymatic activity can be significantly suppressed above the lower critical solution temperature of supramolecularly conjugated PNIPAM, possibly duet oc ollapse of the de-solvated polymer chains on the protein surface.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Redox responsive activity regulation in exceptionally stable supramolecular assembly and co-assembly of a protein

“…In previously reported examples of protein–polymer conjugates, 19 including BSA–polymer conjugates 36 or supramolecularly assembled proteins, 23,37 the enzymatic activity was reported to be retained. In contrast, the present example shows 70–80% inhibition albeit an intact protein secondary structure, indicating the self-assembly provided an effective avenue for encapsulating the protein from the external environment and consequently the substrate had limited access to the active site of the protein.…”

“…In the recent past we have reported 21 supramolecular structure-directing unit (SSDU) regulated entropy driven assembly of hydrophilic polymers by directional molecular interaction in which the self-assembly and morphology of the brush like supramolecular polymer 22 could be regulated by specific molecular interactions instead of the packing parameter. We envisaged this could be equally effective for programmable assembly of SSDU-attached biomacromolecules such as proteins 23 with the potential to address some of the pitfalls of protein–polymer conjugates as discussed before. With this objective, we have synthesized NDI-BSA ( Scheme 1 ) in which a protein Bovine serum albumin (BSA) is attached with a SSDU that consists of a naphthalene-diimide (NDI) chromophore and an amide group.…”

Molecular Recognition Driven Bioinspired Directional Supramolecular Assembly of Amphiphilic (Macro)molecules and Proteins

“…In this context, we envisioned that the conjugation of a protein with a SSDU might be useful for regulating protein assembly. We were successful in the synthesis of NDI-27 (Figure a) in which a hydrazide-containing SSDU was attached to bovine serum albumin (BSA) . It showed entropically favorable highly stable assembly producing nanoparticles ( D h ≈ 30 nm) (Figure b).…”

“…(a) Structure of SSDU-attached BSA systems reported in refs and . Representative TEM images of (b) NDI-27, (c) NDI-28, and (d) NDI-25 + NDI-28 (7:3).…”

“…(f) Relative enzymatic hydrolysis of BSA and its supramolecular assemblies. Adapted with permission from refs and . Copyright 2019 Wiley VCH and Copyright 2021 Royal Society of Chemistry.…”