Recent developments in designing compact biological photoprobes

Amberlyn M. Wands, Jennifer J. Kohler

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Identification and characterization of small molecule-protein interactions are common needs for both basic science and drug discovery programs. Photoaffinity probe molecules (photoprobes) have been used for more than 40 years to label the targets of small molecules, but identification of those targets has remained challenging. Recently, renewed interest in the use of photoprobes has been spurred by the advent of modern mass spectrometry methods that facilitate target identification. In addition, development of new chemoselective labeling reactions (i.e., "click chemistry" approaches) now enables facile purification of photocrosslinked complexes for analysis. Photoprobe technology is being applied for a variety of purposes, including identifying the direct binding partner(s) of a small molecule, obtaining information about the nature of the ligand binding site in the absence of a three-dimensional structure, determining whether ligand binding occurs through a primary or allosteric site, and investigating the specificity determinants of ligand binding. In this chapter, we discuss a selection of compact photoprobes that have been reported in the past 10 years. The chapter describes photoprobes containing each of the three common photoactivatable functional groups-aryl azide, benzophenone, and diazirine. We highlight the molecular design strategies that have yielded functional photoprobes, including compact construction, choice of photoactivatable functional groups, use of tags for chemoselective labeling, and linker design. We conclude by discussing remaining challenges that stand in the way of widespread adoption of photoprobe reagents.

Original languageEnglish (US)
Title of host publicationPhotoaffinity Labeling for Structural Probing Within Protein
PublisherSpringer Japan
Pages45-78
Number of pages34
ISBN (Electronic)9784431565697
ISBN (Print)9784431565680
DOIs
StatePublished - Sep 25 2017

Fingerprint

Ligands
Molecules
Click Chemistry
Diazomethane
Allosteric Site
Azides
Drug Discovery
Mass Spectrometry
Binding Sites
Technology
Labeling
Functional groups
Proteins
Binding sites
Purification
Mass spectrometry
Labels
benzophenone

Keywords

  • Benzophenone
  • Chemoselective
  • Click chemistry
  • Diazirine
  • Ligand binding
  • Photoaffinity
  • Photocrosslinking
  • Proteomics

ASJC Scopus subject areas

  • Medicine(all)
  • Engineering(all)
  • Chemical Engineering(all)

Cite this

Wands, A. M., & Kohler, J. J. (2017). Recent developments in designing compact biological photoprobes. In Photoaffinity Labeling for Structural Probing Within Protein (pp. 45-78). Springer Japan. https://doi.org/10.1007/978-4-431-56569-7_3

Recent developments in designing compact biological photoprobes. / Wands, Amberlyn M.; Kohler, Jennifer J.

Photoaffinity Labeling for Structural Probing Within Protein. Springer Japan, 2017. p. 45-78.

Research output: Chapter in Book/Report/Conference proceedingChapter

Wands, AM & Kohler, JJ 2017, Recent developments in designing compact biological photoprobes. in Photoaffinity Labeling for Structural Probing Within Protein. Springer Japan, pp. 45-78. https://doi.org/10.1007/978-4-431-56569-7_3
Wands AM, Kohler JJ. Recent developments in designing compact biological photoprobes. In Photoaffinity Labeling for Structural Probing Within Protein. Springer Japan. 2017. p. 45-78 https://doi.org/10.1007/978-4-431-56569-7_3
Wands, Amberlyn M. ; Kohler, Jennifer J. / Recent developments in designing compact biological photoprobes. Photoaffinity Labeling for Structural Probing Within Protein. Springer Japan, 2017. pp. 45-78
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