The potential of cross-linking mass spectrometry in the development of protein-protein interaction modulators

Curr Opin Struct Biol. 2023 Oct:82:102648. doi: 10.1016/j.sbi.2023.102648. Epub 2023 Jul 7.

Abstract

Cross-linking mass spectrometry (XL-MS) can provide a wealth of information on endogenous protein-protein interaction (PPI) networks and protein binding interfaces. These features make XL-MS an attractive tool to support the development of PPI-targeting drugs. Though not yet widely used, applications of XL-MS to drug characterization are beginning to emerge. Here, we compare XL-MS to established structural proteomics methods in drug research, discuss the current state and remaining challenges of XL-MS technology, and provide a perspective on the future role XL-MS can play in drug development, with a particular emphasis on PPI modulators.

Keywords: Cross-linking; Mass spectrometry; PPI modulator; PROTAC; Protein–protein interactions.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Linking Reagents / chemistry
  • Mass Spectrometry / methods
  • Protein Binding
  • Protein Interaction Maps*

Substances

  • Cross-Linking Reagents