Photo-cross-linked small-molecule microarrays as chemical genomic tools for dissecting protein-ligand interactions

Naoki Kanoh, Aya Asami, Makoto Kawatani, Kaori Honda, Saori Kumashiro, Hiroshi Takayama, Siro Simizu, Tomoyuki Amemiya, Yasumitsu Kondoh, Satoru Hatakeyama, Keiko Tsuganezawa, Rei Utata, Akiko Tanaka, Shigeyuki Yokoyama, Hideo Tashiro, Hiroyuki Osada

Research output: Contribution to journalArticle

52 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)789-797
Number of pages9
JournalChemistry - An Asian Journal
Volume1
Issue number6
DOIs
Publication statusPublished - 2006
Externally publishedYes

Fingerprint

Microarrays
Ligands
Molecules
Structure-Activity Relationship
Biological Products
Immobilization
Carrier Proteins
Proteins
Pharmaceutical Preparations
Functional groups
Screening
Experiments
carbene
Irradiation

Keywords

  • Immobilization
  • Ligand screening
  • Microarrays
  • Small molecules
  • Structure-activity relationships

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Photo-cross-linked small-molecule microarrays as chemical genomic tools for dissecting protein-ligand interactions. / 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.

In: Chemistry - An Asian Journal, Vol. 1, No. 6, 2006, p. 789-797.

Research output: Contribution to journalArticle

Kanoh, N, Asami, A, Kawatani, M, Honda, K, Kumashiro, S, Takayama, H, Simizu, S, Amemiya, T, Kondoh, Y, Hatakeyama, S, Tsuganezawa, K, Utata, R, Tanaka, A, Yokoyama, S, Tashiro, H & Osada, H 2006, 'Photo-cross-linked small-molecule microarrays as chemical genomic tools for dissecting protein-ligand interactions', Chemistry - An Asian Journal, vol. 1, no. 6, pp. 789-797. https://doi.org/10.1002/asia.200600208
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. / Photo-cross-linked small-molecule microarrays as chemical genomic tools for dissecting protein-ligand interactions. In: Chemistry - An Asian Journal. 2006 ; Vol. 1, No. 6. pp. 789-797.
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