Unveiling BCL-xL-specific PROTAC efficiency and dissociation pathways using native mass spectrometry

Mohamed I. Gadallah; Kailyn L. Nonhof; Digant Nayak; P. Zhang; Olivia E. Dioli; Guangrong Zheng; Shaun K. Olsen; D. Zhou; Jennifer S. Brodbelt

doi:10.1039/d5sc07400b

January 1, 2026Chemical ScienceOpen Access

Unveiling BCL-xL-specific PROTAC efficiency and dissociation pathways using native mass spectrometry

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Key Points

The research aims to investigate the efficiency and dissociation pathways of BCL-xL-specific PROTAC using innovative mass spectrometry techniques.
Utilized native mass spectrometry to study PROTAC binding and ternary complex formation.
Applied gas-phase activation techniques including collision-induced dissociation (CID) and ultraviolet photodissociation (UVPD).
Employed variable-temperature electrospray ionization (ESI) methods to assess complex stability and disassembly.
Identified the binding characteristics of PROTAC to BCL-xL and the formation of ternary complexes.
Demonstrated the influence of temperature and activation methods on the stability of these complexes.
Revealed stepwise dissociation pathways of PROTAC-induced ternary complexes during analysis.

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Implication

Native mass spectrometry delineates PROTAC binding and dissociation pathways, indicating complex stability.

Abstract

Native mass spectrometry captures PROTAC binding and ternary complex formation, and gas-phase activation (CID, UVPD) and variable-temperature ESI methods delineate the stabilities and stepwise disassembly of PROTAC-induced ternary complexes.

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Gadallah et al. (2026) studied this question.

synapsesocial.com/papers/69994c38873532290d020914 https://doi.org/10.1039/d5sc07400b

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Unveiling BCL-xL-specific PROTAC efficiency and dissociation pathways using native mass spectrometry

Key Points

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Abstract

Discussion

Cite This Study

Unveiling BCL-xL-specific PROTAC efficiency and dissociation pathways using native mass spectrometry

Key Points

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Implication

Abstract

Discussion

Cite This Study

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