Premium
NMR ‐based Fragment Screening of Inhibitors Against p300 CH1 and HIF ‐1α CTAD Interaction
Author(s) -
Eo Yumi,
Shim Myungbo,
Phuong Thuy Nguyen Thi,
Hoa Phuong Pham,
Ahn DaeRo,
Ahn HeeChul
Publication year - 2016
Publication title -
bulletin of the korean chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.237
H-Index - 59
ISSN - 1229-5949
DOI - 10.1002/bkcs.10907
Subject(s) - chemistry , heteronuclear single quantum coherence spectroscopy , nuclear magnetic resonance spectroscopy , protein–protein interaction , proton nmr , biophysics , biochemistry , stereochemistry , biology
NMR spectroscopy of p300 CH1 and HIF ‐1α CTAD complex was conducted to investigate the conformational status of the complex and to screen the protein–protein interaction inhibitors. The individual p300 CH1 and HIF ‐1α CTAD were unstructured or partially structured; however, the complex had well‐defined folded structure. Since the 1 H‐ 15 N HSQC spectrum of p300 CH1 or HIF ‐1α CTAD in the free state was completely different from that in the bound state, it was possible to discriminate whether the protein was in the complex state or not. Fragment compounds were titrated to p300 CH1 and HIF ‐1α CTAD complex and some showed inhibition of protein–protein interaction based on the analyses of NMR spectra. The result shows that NMR ‐based screening is possible to discover the fragment chemicals which inhibit the formation of p300 CH1 and HIF ‐1α CTAD complex.