Raman spectroscopy platform for screening SGLT1 and GLUT5 transporter modulators

Overview

This solution offers a non-radioactive alternative to traditional transporter uptake assays, using alkyne-labelled substrates and Raman spectroscopy to study membrane transporter function. The platform is being applied to two clinically important human sugar transporters: SGLT1 (sodium-glucose co-transporter 1) and GLUT5 (fructose transporter). Both are relevant targets in metabolic disease research, including diabetes, obesity, and related disorders, where identifying compounds that modulate sugar uptake is of significant therapeutic interest.

By eliminating the need for radiolabelled substrates, the approach reduces regulatory burden, safety concerns, and disposal costs associated with radioactive assays, while delivering comparable specificity and sensitivity. The technology is designed to be transferable to any membrane transporter, opening a broad route for compound screening across transporter biology.

Technical specifications

Core method:

• Alkyne-labelled glucose and fructose substrates carry a unique Raman spectroscopic signature that is easily detected against biological background
• Heterologous expression of SGLT1 and GLUT5 in E. coli enables controlled uptake studies
• Raman spectroscopy quantifies substrate uptake and detects competition from non-labelled competitor molecules
• Validated specificity: the platform has already demonstrated that non-substrate molecules do not produce false signals

Key advantages:

• No radiolabels required, removing radiation safety, licensing, and waste disposal requirements
• Suitable for high-throughput screening of inhibitor and promoter compound libraries
• Adaptable to mammalian cell expression if bacterial expression is not viable
• Applicable to a wide range of membrane transporters beyond SGLT1 and GLUT5

Development pathway:

• 0–6 months: Express SGLT1 and GLUT5 in E. coli and optimise Raman uptake assays, with mammalian cell expression as a fallback option
• 6–24 months: Screen sponsor-defined compound catalogues to identify modulators, refine methodology, and extend the platform to additional transporters and host systems

Technology readiness level

The underlying Raman spectroscopy method with alkyne-labelled substrates has been validated using a pathogen-derived purine transporter (ThNTT4) expressed in E. coli. Results confirmed statistically significant transport of alkyne-labelled ATP, successful competition by excess non-labelled ATP, and specificity demonstrated by the absence of transport for non-substrate molecules. This validation work is currently in press.

Application of the platform to SGLT1 and GLUT5 is at an early stage, beginning with expression and assay optimisation in the first six months. The team brings 18 years of experience in mammalian cell expression as a contingency route. The approach is positioned at a technology readiness level suitable for collaborative development with industry partners interested in metabolic disease drug discovery, nutritional science, or broader transporter biology applications.