Molecules that are fundamental to various fields such as pharmaceutical sciences and materials engineering, are synthesized through structural transformations via chemical reactions. The recent advancement in the fields has increased the demand for complex and sophisticated molecules, necessitating the reactions applicable to highly functionalized molecules. In this context, chemical transformation with the selectivity such as substrate- or regio-selectivities holds promise for the feasibility of molecules with more advanced designs.
Amyloids are self-assembled molecules in which β-sheets in peptides are perpendicularly stacked. Many planary structures are known for binding with the β-sheets paticular to amyloids. In this work, we have uncoverd that amyloids control the selectivity of chemical reactions for substrates bearing azo-stilben moiety (ASB) via amyloid-substrate complex.
(A)Catalysis driven by amyloid-substrate complex (CASL)1
Amyloid composed of Ac-NFGAIL-NH2 hexapeptide (NL6) promoted modification of the amine functionality tethered by ASB in acidic buffer. Crystallographic study revealed that the amide bond at Phe-Gly residues in NL6 activated the amine by proximity effect via the amyloid-ASB complex. Following the catalytic mechanism, NL6 enabled substrate-selective modification of amines. Specifically, the amine on ASB was modified, while the seven-amines in lysozyme remained intact.
(B) Amyloid-reoriented enzyme catalysis2
We discovered that amyloid composed of Bz-FFAALL-NH2 hexapeptide (BL7) prevented the substrate from enzyme approaching by forming amyloid-ASB complex. According to the ASB-bound protection, the site close to ASB was protected by BL7, while enzyme catalysis was active at sites remote to ASB. Consequently, regio-selective enzyme catalysis was achieved. This demonstrated utilizing amyloids provided regio-selectivity in enzyme catalysis.