An RNA aptamer that selectively inhibits the enzymatic activity of protein tyrosine phosphatase 1B in vitro.
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.
Townshend
Brent
B
Aubry
Isabelle
I
Marcellus
Richard C
RC
Gehring
Kalle
K
Tremblay
Michel L
ML
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
D052157:Aptamers, Nucleotide; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1