title: Substrate specificity of an actively assembling amyloid catalyst.
abstract: In the presence of Zn2+, the catalytic, amyloid-forming peptide Ac-IHIHIQI-NH2, was found to exhibit enhanced selectivity for hydrophobic p-nitrophenyl ester substrates while in the process of self-assembly. As opposed to the substrate p-nitrophenyl acetate, which was more effectively hydrolyzed with Ac-IHIHIQI-NH2in its fully fibrillar state, the hydrophobic substrate Z-L-Phe-ONp was converted with a second-order rate constant more than 11-times greater when the catalyst was actively assembling. Under such conditions, Z-L-Phe-ONp hydrolysis proceeded at a greater velocity than the more hydrophilic and otherwise more labile ester Boc-L-Asn-ONp. When assembling, the catalyst also showed increased selectivity for the L-enantiomer of Z-Phe-ONp. These findings suggest the occurrence of increased interactions of hydrophobic moieties of the substrate with exposed hydrophobic surfaces of the assembling peptides and present valuable features for future de novo design consideration.
authors.affiliation: Freie Universität Berlin Department of Biology, Chemistry, Pharmacy Institute of Chemistry and Biochemistry Berlin, Germany.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Heier
authors.affiliation: Freie Universität Berlin Department of Biology, Chemistry, Pharmacy Institute of Chemistry and Biochemistry Berlin, Germany.
authors.forename: Dorian J
authors.initials: DJ
authors.lastname: Mikolajczak
authors.affiliation: Freie Universität Berlin Department of Biology, Chemistry, Pharmacy Institute of Chemistry and Biochemistry Research Center for Electron Microscopy Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Böttcher
authors.affiliation: Freie Universität Berlin Department of Biology, Chemistry, Pharmacy Institute of Chemistry and Biochemistry Berlin, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Koksch
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D002942:Circular Dichroism; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity; D015032:Zinc / Q000737:chemistry
chemical_list: D010455:Peptides; D015032:Zinc
keywords: catalysis; de novo; peptide; self-assembly; zinc-bound hydroxide