Scientists develop investigations to drive the discovery of new drugs

A study by the University of Loughborough and the University of Oxford in England has led to the development of small molecule probes that can deepen the understanding of important cellular messengers and lead to the development of new therapeutic drugs.

The research paper features the researchers’ groundbreaking investigation of binding to inositol pyrophosphate or 5-PP-InsP₅.

5-PP-InsP₅ plays a fundamental role in a variety of biological processes, including cell growth, programmed cell death, and enzyme regulation, and new roles are still emerging with the recently discovered primary regulator of blood glucose levels.

Due to its diverse roles in cellular processes, 5-PP-InsP₅ are attractive targets for developing therapeutic drugs.

However, biomedical research and drug discovery rely on ‘small molecule probes’ to detect specific target molecules and, until now, no 5-PP-InsP₅– special probes exist.

The research team of Stephen Butler, Felix Plasser, and Barry Potter combined their synthetic and computational chemistry modeling knowledge to create a custom probe for 5-PP-InsP₅ which emits a bright red light upon binding.

The intensity and duration of this light can be measured to measure 5-PP-InsP levels₅ during different biological processes, paving the way for a deeper understanding of their precise function, mechanism and therapeutic potential.

Butler said: “A key motivation in our lab is to develop molecular tools with real-world applications, so we are excited about the potential of the investigation reported here as a drug discovery tool, which could enable high-throughput screening of drug-like molecules that modulate different biological processes. involving the cellular messenger 5-PP-InsP_5.

“Other inositol pyrophosphates exist and are still emerging in biology, so methods to detect, synthesize and exploit these are also needed and will be facilitated by the design features of the probes created in this project.”

Potter added: “I have spent most of my independent scientific career in research on inositol phosphate and feel that the emergence of this new pyrophosphate messenger, with its emerging biological function, is truly exciting for the field and calls for innovation.

“Our new, highly collaborative paper presents a very timely technique for measuring such messengers for the first time and should enable many further developments in the area.”

The study’s co-authors are Megan Shipton and Fathima Jamion, a PhD student and final year scholar from Oxford and Loughborough, respectively.

Research paper, Wise synthesis and luminescence sensing of the cellular messenger inositol pyrophosphate 5-PP-InsP₅funded by UKRI Biotechnology and Biotechnological Sciences Research Council (Butler) and The Wellcome Trust (Potter).