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S ubstrate specificity of an actively assembling amyloid catalyst
Author(s) -
Heier Jason L.,
Mikolajczak Dorian J.,
Böttcher Christoph,
Koksch Beate
Publication year - 2017
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.23003
Subject(s) - chemistry , catalysis , amyloid (mycology) , amyloid fibril , amyloid β , biophysics , biochemistry , inorganic chemistry , medicine , disease , pathology , biology
In the presence of Zn 2+ , the catalytic, amyloid‐forming peptide Ac‐IHIHIQI‐NH 2 , 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‐NH 2 in 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.