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Related Experiment Video

Updated: Jun 11, 2026

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

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Published on: November 9, 2020

Degrading Resistance on Command: LAMP-D Reframes Targeted Protein Degradation as a Photochemical Problem.

Ashwini Kumar¹, Md Kausar Raza²

¹James Tarpo Jr. and Margaret Tarpo Department of Chemistry, Purdue University, West Lafayette, Indiana, USA.

|June 9, 2026

Summary

Researchers developed light-activated metal-dependent protein degradation (LAMP-D) to eliminate bacterial enzymes like New Delhi metallo-β-lactamase 1 (NDM-1). This novel method bypasses cellular machinery, offering a new strategy against antimicrobial resistance.

Keywords:

NDM‐1 antimicrobial resistance photodynamic therapy ruthenium photosensitizer targeted protein degradation

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Area of Science:

Biochemistry
Molecular Biology
Drug Discovery

Background:

Antimicrobial resistance (AMR) necessitates novel therapeutic approaches beyond enzyme inhibition.
Targeted protein elimination is an emerging strategy to combat resistant bacteria.

Purpose of the Study:

To introduce and validate a light-activated metal-dependent protein degradation (LAMP-D) system.
To demonstrate the degradation of New Delhi metallo-β-lactamase 1 (NDM-1) using LAMP-D.

Main Methods:

Development of a ruthenium photosensitizer tethered to a targeting ligand for NDM-1.
Application of blue light to activate photochemical degradation of NDM-1.
In vitro and in vivo testing in Escherichia coli (E. coli).

Main Results:

Light-triggered degradation of NDM-1 was achieved via LAMP-D.
>100-fold enhancement in NDM-1 enzyme inhibition in vitro.
53-fold rescue of meropenem activity in E. coli without cytotoxicity.

Conclusions:

LAMP-D offers a novel, light-driven approach for targeted protein degradation.
This method bypasses the need for endogenous ligases, proteasomes, or ternary complex formation.
LAMP-D presents a promising strategy for combating antimicrobial resistance, particularly in Gram-negative pathogens.