An RNA Aptamer That Selectively Inhibits the Enzymatic Activity of Protein Tyrosine Phosphatase 1B in vitro

作者：Townshend Brent^*; Aubry Isabelle; Marcellus Richard C; Gehring Kalle; Tremblay Michel L

来源：ChemBioChem, 2010, 11(11): 1583-1593.

DOI：10.1002/cbic.201000208

• aptamers
• enzymes
• inhibitors
• protein tyrosine phosphatases
• SELEX

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 K(i), 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.

• 出版日期2010-7-26