Structural insights into the design of nonpeptidic isothiazolidinone-containing inhibitors of protein-tyrosine phosphatase 1B.

@article{Ala2006StructuralII,
  title={Structural insights into the design of nonpeptidic isothiazolidinone-containing inhibitors of protein-tyrosine phosphatase 1B.},
  author={Paul J Ala and Lucie Gonneville and Milton C Hillman and Mary Becker-Pasha and Eddy W. Yue and Brent D Douty and Brian Wayland and Padmaja Polam and Matthew Lantz Crawley and Erin E McLaughlin and Richard B Sparks and Brian Glass and Amy G Takvorian and Andrew P. Combs and Timothy C. Burn and Gregory F. Hollis and Richard Wynn},
  journal={The Journal of biological chemistry},
  year={2006},
  volume={281 49},
  pages={38013-21}
}
Structural analyses of the protein-tyrosine phosphatase 1B (PTP1B) active site and inhibitor complexes have aided in optimization of a peptide inhibitor containing the novel (S)-isothiazolidinone (IZD) phosphonate mimetic. Potency and permeability were simultaneously improved by replacing the polar peptidic backbone of the inhibitor with nonpeptidic moieties. The C-terminal primary amide was replaced with a benzimidazole ring, which hydrogen bonds to the carboxylate of Asp(48), and the N… CONTINUE READING