Model of Intermolecular Interactions between High Affinity Phosphopeptides and Stat3

  • John S. McMurray
  • Zhiyong Ren
  • Pijus K. Mandal
  • Xiaomin Chen
Part of the Advances in Experimental Medicine and Biology book series (volume 611)


Signal transducer and activator of transcription (Stat3) is constitutively active in several cancer types and it participates in the increased transcription of cell cycling, survival, and angiogenesis genes. Therefore Stat3 is a target for anti-cancer drug design [1]. Compounds targeted to the SH2 domain of Stat3 would uncouple this protein from its aberrant activity by preventing recruitment to receptors, blocking reciprocal pTyr-SH2 domain dimerization, translocation to the nucleus and DNA binding, thus preventing transcription of the cell-cycling, survival, and angiogenesis genes. To date there are no crystal or NMR structures of high affinity phosphopeptides complexed with the SH2 domain of Stat3 to aid in inhibitor design.

Stat3 binds phosphopepties in the context of pYXXQ. Structure activity studies suggest that Gln at pY+3 is optimal [2]. A model of our lead peptide, pYLPQTV, would be helpful in revealing the interactions between the specificity determinant Gln and...


Specificity Determinant Side Chain Carboxyl Docking Module Main Chain Carbonyl Main Chain Conformation 
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This work was supported by the National Cancer Institute (CA096652) and the M. D. Anderson Cancer Center University Cancer Fund. The NCI Cancer Center Support Grant CA016672 is gratefully acknowledged for the support of our molecular modeling software and hardware.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • John S. McMurray
    • 1
  • Zhiyong Ren
    • 2
  • Pijus K. Mandal
    • 1
  • Xiaomin Chen
    • 2
  1. 1.Department of Experimental TherapeuticsThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  2. 2.Department of Biochemistry and Molecular BiologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA

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