Identification of small molecule proliferating cell nuclear antigen (PCNA) inhibitor that disrupts interactions with PIP-box proteins and inhibits DNA replication.

@article{Punchihewa2012IdentificationOS,
  title={Identification of small molecule proliferating cell nuclear antigen (PCNA) inhibitor that disrupts interactions with PIP-box proteins and inhibits DNA replication.},
  author={Chandanamali Punchihewa and Akira Inoue and Asami Hishiki and Yoshihiro Fujikawa and Michele Connelly and Benjamin J Evison and Youming Shao and Richard H. Heath and Isao Kuraoka and Patrick Rodrigues and Hiroshi Hashimoto and Masanobu Kawanishi and Mamoru Sato and Takashi Yagi and Naoaki Fujii},
  journal={The Journal of biological chemistry},
  year={2012},
  volume={287 17},
  pages={14289-300}
}
We have discovered that 3,3',5-triiodothyronine (T3) inhibits binding of a PIP-box sequence peptide to proliferating cell nuclear antigen (PCNA) protein by competing for the same binding site, as evidenced by the co-crystal structure of the PCNA-T3 complex at 2.1 Å resolution. Based on this observation, we have designed a novel, non-peptide small molecule PCNA inhibitor, T2 amino alcohol (T2AA), a T3 derivative that lacks thyroid hormone activity. T2AA inhibited interaction of PCNA/PIP-box… CONTINUE READING
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