title: Catalytic DNA with phosphatase activity.
abstract: Catalytic DNA sequences (deoxyribozymes, DNA enzymes, or DNAzymes) have been identified by in vitro selection for various catalytic activities. Expanding the limits of DNA catalysis is an important fundamental objective and may facilitate practical utility of catalysts that can be obtained from entirely unbiased (random) sequence populations. In this study, we show that DNA can catalyze Zn(2+)-dependent phosphomonoester hydrolysis of tyrosine and serine side chains (i.e., exhibit phosphatase activity). The best deoxyribozyme decreases the half-life for phosphoserine hydrolysis from as high as >10(10) y to <1 h. The phosphatase activity also occurs with nonpeptidic substrates but with reduced efficiency, indicating a preference for phosphopeptides. The newly identified deoxyribozymes can function with multiple turnover using free peptide substrates, have activity in the presence of human cell lysate or BSA, and catalyze dephosphorylation of a larger protein substrate, suggesting broader application of DNA catalysts as artificial phosphatases.
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Jagadeeswaran
authors.initials: J
authors.lastname: Chandrasekar
authors.forename: Scott K
authors.initials: SK
authors.lastname: Silverman
mesh_terms: D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D021881:DNA, Catalytic / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006207:Half-Life; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D013058:Mass Spectrometry; D009841:Oligonucleotides / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D012394:Rosaniline Dyes
chemical_list: D021881:DNA, Catalytic; D009841:Oligonucleotides; D012394:Rosaniline Dyes; C005095:malachite green; D010768:Phosphoserine; D019000:Phosphotyrosine; D010744:Phosphoric Monoester Hydrolases