Journal
CHEMBIOCHEM
Volume 11, Issue 11, Pages 1583-1593Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201000208
Keywords
aptamers; enzymes; inhibitors; protein tyrosine phosphatases; SELEX
Funding
- Canadian Institutes of Health Research [MOP-62887]
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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.
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