Allosterically Regulated Phosphatase Activity from Peptide-PNA Conjugates Folded Through Hybridization.
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.
Department of Organic Chemistry, NCCR Chemical Biology, University of Geneva, Quai Ernest Ansermet 30, 1211, Geneva, Switzerland.
Takuya
T
Machida
Department of Organic Chemistry, NCCR Chemical Biology, University of Geneva, Quai Ernest Ansermet 30, 1211, Geneva, Switzerland.
Som
S
Dutt
Department of Organic Chemistry, NCCR Chemical Biology, University of Geneva, Quai Ernest Ansermet 30, 1211, Geneva, Switzerland. nicolas.winssinger@unige.ch.
Nicolas
0000-0003-1636-7766
N
Winssinger
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D055162:Biocatalysis; D020134:Catalytic Domain; D005456:Fluorescent Dyes / Q000737:chemistry; D006868:Hydrolysis; D009693:Nucleic Acid Hybridization; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013379:Substrate Specificity
D005456:Fluorescent Dyes; D020135:Peptide Nucleic Acids; D010455:Peptides; D010744:Phosphoric Monoester Hydrolases
PNA; catalysis; peptides; system chemistry