title: Photo-cross-linked small-molecule microarrays as chemical genomic tools for dissecting protein-ligand interactions.
abstract: 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.
authors: Antibiotics Laboratory, Discovery Research Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. hisyo@riken.jp
authors: Naoki
authors: N
authors: Kanoh
authors: Aya
authors: A
authors: Asami
authors: Makoto
authors: M
authors: Kawatani
authors: Kaori
authors: K
authors: Honda
authors: Saori
authors: S
authors: Kumashiro
authors: Hiroshi
authors: H
authors: Takayama
authors: Siro
authors: S
authors: Simizu
authors: Tomoyuki
authors: T
authors: Amemiya
authors: Yasumitsu
authors: Y
authors: Kondoh
authors: Satoru
authors: S
authors: Hatakeyama
authors: Keiko
authors: K
authors: Tsuganezawa
authors: Rei
authors: R
authors: Utata
authors: Akiko
authors: A
authors: Tanaka
authors: Shigeyuki
authors: S
authors: Yokoyama
authors: Hideo
authors: H
authors: Tashiro
authors: Hiroyuki
authors: H
authors: Osada
mesh_terms: D001667:Binding, Competitive; D003432:Cross-Linking Reagents / Q000737:chemistry*; D023281:Genomics / Q000379:methods*; D005898:Glass; D006838:Hydrocarbons / Q000737:chemistry; D008024:Ligands; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D019920:Photoaffinity Labels / Q000737:chemistry; D010777:Photochemistry; D040081:Protein Array Analysis; D011506:Proteins / Q000737:chemistry*; D011869:Radioligand Assay; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014466:Ultraviolet Rays
chemical_list: D003432:Cross-Linking Reagents; D006838:Hydrocarbons; D008024:Ligands; D019920:Photoaffinity Labels; D011506:Proteins; C030011:carbene; D008697:Methane