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Photo‐Cross‐Linked Small‐Molecule Microarrays as Chemical Genomic Tools for Dissecting Protein–Ligand Interactions
Author(s) -
Kanoh Naoki,
Asami Aya,
Kawatani Makoto,
Honda Kaori,
Kumashiro Saori,
Takayama Hiroshi,
Simizu Siro,
Amemiya Tomoyuki,
Kondoh Yasumitsu,
Hatakeyama Satoru,
Tsuganezawa Keiko,
Utata Rei,
Tanaka Akiko,
Yokoyama Shigeyuki,
Tashiro Hideo,
Osada Hiroyuki
Publication year - 2006
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.200600208
Subject(s) - small molecule , pharmacophore , chemistry , molecule , ligand (biochemistry) , dna microarray , combinatorial chemistry , protein microarray , computational biology , biophysics , stereochemistry , biochemistry , biology , receptor , organic chemistry , gene , gene expression
We have developed a unique photo‐cross‐linking approach for immobilizing a variety of small molecules in a functional‐group‐independent manner. Our approach depends on the reactivity of the carbene species generated from trifluoromethylaryldiazirine upon UV irradiation. It was demonstrated in model experiments that the photogenerated carbenes were able to react with every small molecule tested, and they produced multiple conjugates in most cases. It was also found in on‐array immobilization experiments that various small molecules were immobilized, and the immobilized small molecules retained their ability to interact with their binding proteins. With this approach, photo‐cross‐linked microarrays of about 2000 natural products and drugs were constructed. This photo‐cross‐linked microarray format was found to be useful not merely for ligand screening but also to study the structure–activity relationship, that is, the relationship between the structural motif (or pharmacophore) found in small molecules and its binding affinity toward a protein, by taking advantage of the nonselective nature of the photo‐cross‐linking process.