Journal of Computer-Aided Molecular Design

, Volume 21, Issue 10–11, pp 641–648 | Cite as

Computational study on mechanism of G-quartet oligonucleotide T40214 selectively targeting Stat3

  • Qiqing Zhu
  • Naijie Jing


The mounting evidences have shown that signal transducer and activator of transcription 3 (Stat3) is a critical target for cancer therapy. Recently, we developed a G-quartet oligonucleotide T40214 as a novel and potent Stat3 inhibitor. T40214 specifically inhibited DNA-binding activity of Stat3 and significantly suppressed the growth of many tumor xenografts in nude mice. To determine the mechanism of GQ-ODNs selectively targeting Stat3, we established a 3D model of complex T40214/p-Stat3 dimer based on experimental evidences. The binding site of T40214 within Stat3 dimer was determined by statistical docking analysis. The results indicated that T40214 strongly interacted within the region from residue E638 through E652 of Stat3 dimer. The binding model refined by Hex docking disclosed that T40214 binds to SH2 domain of Stat3 and forms H-bonds with residues Q643, Q644, N646, and N647, which are critical for the binding interaction. The 3D models also suggested that T40214 inhibits Stat3 activity through disrupting the binding interaction between Stat3 dimer and DNA duplex for transcription. Our computational studies provided a platform for future structure-based drug design of novel Stat3 inhibitors.


Stat3 Stat1 Molecular docking T40214 GQ-ODN 



The authors wish to thank Yidong Li, who contributed to this study by providing the EMSA results. This project was supported by the following grants: CA104035 (NIH) and competitive award from Prostate Cancer Foundation. In addition, Dr. Zhu received support through NIH training grant T32 DK60445.


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Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  1. 1.Department of MedicineBaylor College of MedicineHoustonUSA
  2. 2.Cancer CenterBaylor College of MedicineHoustonUSA

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