![]() Supercharging proteins and polypeptides thus provides materials with exciting properties such as hyper-temperature resistance 7 and the ability of overcoming biological barriers in vivo. All these features are far beyond what is possible with conventional polyelectrolyte polymers. Finally, supercharged proteins are genetically encoded, allowing their production in a target cell. Moreover, various charge-induced interactions can be incorporated in these types of materials and the supercharged proteins can be easily fused to other proteins encoding additional functionalities. Control over its primary structure provides the ability to regulate the charge density, molecular weight, and the position of charges along the backbone of supercharged proteins and polypeptides. By supercharging, features of proteins can be improved or new functions can be achieved. Therefore, supercharging proteins and polypeptide chains has attracted great interest in recent years. Natural supercharged proteins can be an inspiration for chemists, material scientists, and protein engineers to design new materials with attractive properties. 5, 6 Thereby, natural supercharged proteins harbor essential functions for biology. The supercharged unstructured proteins steer phase separations, provide mechanical properties, and assist in calcium storage of cells. ![]() A large number of natively supercharged proteins have a disordered structure. 4 The supercharged proteins in a folded state have important biological functions, including DNA binding, transcription regulation, protein synthesis, antimicrobial activity, and signal transduction. Supercharged proteins are a class of proteins defined as more than one net charge per kilodalton of molecular weight and can be categorized into folded and unstructured entities. 1, 3 The charge of a protein is further modulated by the pH and protic amino acids such as tyrosine and cysteine that can become charged depending on the neighboring amino acids. 1, 2 The amino acids (AAs) that determine the charge of the protein are cationic Lys/Arg/His and anionic Glu/Asp residues. The other important class of biomacromolecules, i.e., proteins, can be either positively or negatively charged. For example, the carrier of genetic information and its transcribed products, DNA and RNA, are nucleic acids bearing negative charges along the backbone. ![]() These electrostatic forces play an important role in living cells where charged molecules are omnipresent. Moreover, potential applications are highlighted and challenges are discussed.Ĭoulomb's law is a fundamental law in our universe, which states that opposite charges attract each other and like charges repel each other in a distance-dependent manner. Their synthesis, structures, and properties are summarized. Supercharged proteins and SUPs are developed into exciting classes of materials. These coacervates can even be directly generated in living cells or can be combined with dissipative fiber assemblies that induce life-like features. Interestingly, SUPs undergo fluid–fluid phase separation to form coacervates. These architectures represent novel bulk materials that are sensitive to external stimuli. ![]() SUPs can also be complexed with artificial entities to yield thermotropic and lyotropic liquid crystals and liquids. Genetically engineered, supercharged unstructured polypeptides (SUPs) are just one promising fusion tool. One elegant method to transfer the favorable properties of supercharged proteins to other proteins is the fabrication of fusions. Recent findings show that supercharging proteins allows for control of their properties such as temperature resistance and catalytic activity. Natural proteins with a high net charge exist in a folded state or are unstructured and can be an inspiration for scientists to artificially supercharge other protein entities. Biomacromolecules such as proteins are orchestrated by electrostatics, among other intermolecular forces, to assemble and organize biochemistry. Electrostatic interactions play a vital role in nature. ![]()
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