Small molecule modulation of protein polymerization

Abstract

Small molecules have been shown to not only mediate and enhance polymerization, in a manner analogous to a surface residue mutation or post-translational modification, but also bind and stabilize the repeating unit to inhibit self-assembly.

Plant Protein‐Peptide Supramolecular Polymers with Reliable Tissue Adhesion for Surgical Sealing

“…[1][2][3][4][5] These systems have served as sources of inspiration for scientists to manipulate the assembly and supramolecular polymerization of proteins with the aim to create artificial biomaterials that can mimic, recapitulate or even surpass the key features of natural systems. [6][7][8][9][10][11] For that purpose, an effective and commonly used way is incorporating proteins with small molecule ligands, [12][13][14] polymers, [15][16][17] nanoparticles, [18][19][20] nucleic acids, [21] proteins, [22][23][24] and peptides. [25,26] Among them, the fusion of protein and peptide is becoming an emerging frontier in this field due to the tunable chemical, physical and biological features of peptide segments.…”

Unnaturally Distorted Hexagonal Protein Ring Alternatingly Reorganized from Two Distinct Chemically Modified Proteins

“…Recently, chemical modification techniques are being applied to disrupt or promote the assembling process of natural proteins by directly adjusting the PPIs with the conjugated artificial components. 26,27 In these studies, however, the introduced chemical ligands do not modify the shape or the order from the natural assembly. Our previous study had shown that chemical modification of the protein interface facilitates the reassembly of mutationally disassembled peroxiredoxin (Prx) protein into its native structure.…”

“…Artificial design of PPIs, that enable the formation of novel protein assemblies and interprotein communications, is a challenging task, especially for developing functional and therapeutic biomaterials. − Therefore, PPIs have been enthusiastically redesigned using rational design and computer-guided mutagenesis, generating homo- and heteroboundaries of multiple protein chains. − Conventional techniques have relied on the 20 canonical amino acids, and, though these earlier methods have been beneficial, expansion of proteins’ structural and functional diversity necessitated incorporation of additional components. Recently, chemical modification techniques are being applied to disrupt or promote the assembling process of natural proteins by directly adjusting the PPIs with the conjugated artificial components. , In these studies, however, the introduced chemical ligands do not modify the shape or the order from the natural assembly. Our previous study had shown that chemical modification of the protein interface facilitates the reassembly of mutationally disassembled peroxiredoxin (Prx) protein into its native structure .…”