Hi there! Today's short post is about usage of proteins as a generic scaffolds for designing chemical reactors.
Many good chemistries can not be simply accomplished in the tube because in order to proceed these reactions require very special conditions, such as presence of a metal in a certain oxidized state, or whole reaction should be shielded from the water solution since very unstable intermediate complex is formed during the reaction path. Thus having a nanoreactors with controllable conditions is a target of many chemists nowadays. There were numerous attempts to build such things out of complex organic molecules, however every single one needs a special approach and therefore lot's of effort. In contrast, mother nature successfully solved this problem (and keeps solving it) with proteins - the most generic chemical reactor. The reactions centers of many enzymes provide special conditions such as high hydrophobicity (lack of water molecules), or positioning of these water molecules in a reaction-favorable places. Upon finishing the reactions, active site of a protein will be freed from the product due to the special its characteristics. Thus some of the enzymes are able to perform reaction up to million times per second (turnover rate for carboanhydrase is half a million!) - much faster than chemistry in homogeneous environment would allow.
This time a group from University of Basel under the leadership of Professor Nico Bruns used a protein that normally helps other proteins to fold (chaperonin) as a nanoreactor for polymerization. These sort of proteins form hydrophobic pores that are large enough to let macromolecules enter and leave it. Thus authors conjectured that this would be a perfect scaffold for assisting polymerization reaction. They simply modified chaperonin mutant cysteine residue with EDTA-like compound what let the catalytic Copper ion to be trapped inside the cavity, whereas monomers were allowed to enter the pore by diffusion. As a result they were able to obtain polymer with very low polydispercity index.
Another example, probably less successful (that's why it is in 'Chembiochem', not in the 'Angewandte chemie' where previous paper appeared) but still interesting. Group of chemists under the supervison of Prof. Jared C. Lewis from University of Chicago introduced metal ions into protein scaffolds via unnatural aminoacids. Firstly they synthesized a protein containing clickable amino acid ( Azidophenylalanine) via reassigning the amber-codon (pEVOL system, developed by Prof. Peter G. Schultz). Then they coupled a number of BCN-linked organic ligands to the protein via Strain Promoted Azyde-Alkyne Cycloadition (SPAAC). Ligands in turn could form a complex with metals such as Rhodium, Manganese and Copper. Although authors could not reach anticipated velocities of some of the reactions they still were able to demonstrate the possibility to build such artificial metallo-enzymes. May be use of other protein scaffolds (such as mentioned above chaperonin) with computational design aid (or probably directed evolution) could help us to get very active enzymes for biotech and pharma industry in future.
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