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Phosphotyrosyl mimetics in the development of signal transduction inhibitors

  1. Author:
    Burke, T. R.
    Lee, K.

  2. Author Address

    NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21701 USA NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21701 USA Burke TR NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21701 USA
    1. Year: 2003
  2. Journal: Accounts of Chemical Research
    1. 36
    2. 6
    3. Pages: 426-433
  4. Type of Article: Review
  1. Abstract:

    Phosphotyrosyl (pTyr) residues play important roles in cellular signal transduction by facilitating recognition and binding necessary for critical protein-protein interactions, and for this reason pTyr motifs represent attractive starting points in the development of signaling antagonists. Although the pTyr phosphoryl moiety is central in these phenomena, its incorporation into signaling inhibitors is contraindicated due to enzymatic lability and limited bioavailabilty associated with phosphate esters. To address these limiations, an entire field of study has arisen devoted to the design and utilization of pTyr mimetics. This Account provides a perspective on the roles of pTyr residues in signal transduction and approaches to pTyr mimetic development.

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