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Systemic chemical proteomics based target identification and validation of OMe‐Syn, a new anti‐angiogenic natural small molecule
Author(s) -
Kim Nam Hee,
Pham Ngoc,
Quinn Ronald,
Kwon Ho Jeong
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.612.4
Subject(s) - biopanning , proteomics , angiogenesis , proteome , phage display , chemistry , biochemistry , in vitro , small molecule , peptide library , in vivo , target protein , mechanism of action , biology , peptide sequence , gene , peptide , cancer research , microbiology and biotechnology
Angiogenesis is a new blood vessel formation from existing parent vessel through the generation of endothelial cells. R‐(‐)‐O‐methylsynephrine (OMe‐Syn) is a natural product isolated from a plant of the Rutaceae family. Recently, we found that OMe‐Syn inhibited vascular endothelial growth factor (VEGF)‐induced angiogenesis both in vitro and in vivo . To investigate the mode of action of the compound, identification of the target protein of OMe‐Syn was carried out by using affinity based phage display biopanning. T7 phages encoding human cDNA libraries were used for affinity selection of OMe‐Syn binding protein. After 4th round of biopanning, the OMe‐Syn binding protein (OBP) was discovered as the high affinity binding protein of the compound. Furthermore, cytosolic proteome of OMe‐Syn treated cells was analyzed using differential gel electrophoresis (DIGE) and MALDI‐TOF MS analysis to investigate the mechanism of the compound. Among the proteins affected by OMe‐Syn, proteins responsible for anti‐angiogenic activity of OMe‐Syn are identified and under investigation for their relevancy to the biological activity of OMe‐Syn. Systemic investigation with chemical proteomics on mode of action of bioactive small molecules will provide new insights into the molecular mechanism underlying the biological activity of OMe‐Syn and its target protein. This study is supported by self‐research funding.