title: An RNA aptamer that selectively inhibits the enzymatic activity of protein tyrosine phosphatase 1B in vitro.
abstract: SELEX was used to create an RNA aptamer targeted to protein tyrosine phosphatase 1B (PTP1B), an enzyme implicated in type 2 diabetes, breast cancer and obesity. We found an aptamer that strongly inhibits PTP1B in vitro with a Ki of less than 600 pM. This slow-binding, high-affinity inhibitor is also highly selective, with no detectable effect on most other tested phosphatases and approximately 300:1 selectivity over the closely related TC-PTP. Through controlled synthesis of truncated variants of the aptamer, we isolated shorter forms that inhibit PTP1B. We also investigated various single-nucleotide modifications to probe their effects on the aptamer's secondary structure and inhibition properties. This family of aptamers represents an exciting option for the development of lead nucleotide-based compounds in combating several human cancers and metabolic diseases.
authors.forename: Brent
authors.initials: B
authors.lastname: Townshend
authors.forename: Isabelle
authors.initials: I
authors.lastname: Aubry
authors.forename: Richard C
authors.initials: RC
authors.lastname: Marcellus
authors.forename: Kalle
authors.initials: K
authors.lastname: Gehring
authors.forename: Michel L
authors.initials: ML
authors.lastname: Tremblay
mesh_terms: D052157:Aptamers, Nucleotide / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009690:Nucleic Acid Conformation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D052157:Aptamers, Nucleotide; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1