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Allosterically Regulated Phosphatase Activity from Peptide–PNA Conjugates Folded Through Hybridization
Author(s) -
Machida Takuya,
Dutt Som,
Winssinger Nicolas
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201602751
Subject(s) - peptide , peptide nucleic acid , chemistry , biochemistry , nucleic acid , phosphatase , conjugate , enzyme , mathematical analysis , mathematics
The importance of spatial organization in short peptide catalysts is well recognized. We synthesized and screened a library of peptides flanked by peptide nucleic acids (PNAs) such that the peptide would be constrained in a hairpin loop upon hybridization. A screen for phosphatase activity led to the discovery of a catalyst with >25‐fold rate acceleration over the linear peptide. We demonstrated that the hybridization‐enforced folding of the peptide is necessary for activity, and designed a catalyst that is allosterically controlled using a complementary PNA sequence.