Sequence and Surface Confinement Direct Cooperativity in Catalytic Precision Oligomers
In enzymes, the precise sequence of the protein encodes for specific chain folding to preorganize critical amino acid side chains within defined binding pockets, allowing synergistic catalytic activation pathways to be expressed and triggered. In analogy, in a paper just published in J. Am. Chem. Soc. (https://pubs.acs.org/doi/10.1021/jacs.8b00872), Antony Fernandes, Alain Jonas and Prakash Chandra demonstrate that short synthetic precision oligomers having the optimal sequence of a catalytic triad, spatially arranged by dense surface grafting to form confined cooperative “pockets”, display an up to 5-fold activity improvement compared to a “mismatched” sequence or free oligomers. This work, in part supported by an 'Excellence of Science' EOS project, shows a new way to design multifunctional molecular assemblies in order to control functions at a level approaching biological precision.