Novel Small Molecule Probe Developed by Loughborough University and Oxford Opens New Avenues in Cellular Biology

The researchers’ small molecule probe binding to 5-PP-InsP5 and emitting bright red light. Image generated by Dr Felix Plasser, Loughborough University.

(IN BRIEF) Loughborough University and the University of Oxford have collaborated on a groundbreaking study that has resulted in the development of a small molecule probe. This probe specifically binds to inositol pyrophosphate (5-PP-InsP₅), a crucial cellular messenger involved in various biological processes. The probe emits a bright red light upon binding, allowing researchers to measure and quantify the levels of 5-PP-InsP₅ during different biological processes. This breakthrough has the potential to deepen our understanding of 5-PP-InsP₅‘s functions, mechanisms, and therapeutic potential. The study highlights the importance of interdisciplinary research and offers new possibilities for drug development and cellular biology.

(PRESS RELEASE) LOUGHBOROUGH, 30-May-2023 — /EuropaWire/ — Loughborough University, a public research university and a UK top 10 University, and the University of Oxford have jointly conducted a ground-breaking study resulting in the creation of a small molecule probe that has the potential to enhance our understanding of a crucial cellular messenger and facilitate the development of novel therapeutic drugs.

The research paper, which was recognized as Pick of the Week in the prestigious journal Chemical Science by the Royal Society of Chemistry, showcases the innovative probe designed by the researchers to bind to inositol pyrophosphate, commonly known as ‘5-PP-InsP₅‘.

5-PP-InsP₅ plays a pivotal role in various biological processes, including cell growth, programmed cell death, and enzyme regulation. It has also recently emerged as a key regulator of blood glucose levels, indicating its significance in multiple physiological functions.

Given its diverse roles within cellular processes, 5-PP-InsP₅ presents an attractive target for the development of therapeutic drugs. However, biomedical and drug discovery research necessitates the use of “small molecule probes” to detect specific target molecules, and until now, no 5-PP-InsP₅-specific probes existed.

The research team from Loughborough University and the University of Oxford, comprising Dr. Stephen Butler, Dr. Felix Plasser, and Professor Barry Potter, combined their expertise in chemical synthesis and computational modeling to create a probe that specifically targets 5-PP-InsP₅. Importantly, this probe emits a vibrant red light upon binding.

By measuring the intensity and duration of this light, researchers can quantitatively assess the levels of 5-PP-InsP₅ during different biological processes. This breakthrough paves the way for a deeper understanding of the precise functions, mechanisms, and therapeutic potential of 5-PP-InsP₅.

Of the importance of the research, Dr Stephen Butler commented: “A key motivation in our lab is to develop molecular tools with real-world applications, so we’re excited about the potential of the probe reported here as a drug discovery tool, that could enable high-throughput screening of drug-like molecules that modulate biological processes involving the cellular messenger 5-PP-InsP_5.

“Other inositol pyrophosphates exist and are still emerging in biology, so methods to detect, synthesise and exploit these could also be necessary and will be facilitated by the probe design features established in this project.”

Professor Barry Potter, of the University of Oxford, added: “I have spent almost all of my independent scientific career in research on inositol phosphates and feel that the advent of these new pyrophosphate messengers, with their emerging biological functions, is truly exciting for the field and calls for innovation.

“Our highly collaborative new paper presents a very timely technique to measure such a messenger for the first time and should enable a wealth of further developments in the area.”

The study’s co-lead authors, Megan Shipton and Fathima Jamion, expressed their excitement about the collaborative effort and its implications. Megan, a PhD student from the University of Oxford, and Fathima, a final year undergraduate student from Loughborough University, both stated their delight in contributing to uncovering the biological roles of 5-PP-InsP₅.

This remarkable collaboration between Loughborough University and the University of Oxford underscores the power of interdisciplinary research in pushing the boundaries of scientific knowledge. The development of this specific probe opens up new avenues for investigating the functions and therapeutic applications of 5-PP-InsP₅, potentially leading to groundbreaking advancements in drug development and cellular biology.

Megan and Fathima said of their achievement in a joint statement: “We are delighted to work as part of this collaborative team to take some vital steps in helping further uncover the biological roles of 5-PP-InsP₅.

“It’s especially rewarding to see our combined work published in a top chemistry journal and we look forward to seeing how it fuels future research in this area.”

The research paper, titled Expedient synthesis and luminescence sensing of the inositol pyrophosphate cellular messenger 5-PP-InsP₅, was funded by the UKRI Biotechnology and Biotechnological Sciences Research Council (Butler) and The Wellcome Trust (Potter).

It can be read in its entirety on the Chemical Science webpage.

More information on Dr Butler’s work can be found on his research group website. He is pursuing commercialisation of selected luminescent probes as new bioassay technologies and has developed a patented hydrogel material, in collaboration with Loughborough University’s Dr Helen Willcock to encapsulate a variety of probes for monitoring specific ion levels in samples in real-time.

More details on Professor Potter’s research interests are available on his website. Aside from his work on inositol phosphates he has designed and synthesised novel drugs and brought them to many international clinical trials in both male and female cancer patients with evidence of clinical benefit.

Notes for editors

Press release reference number: 23/82