Scientists have designed a new synthetic glucose binding molecule platform that brings us one step closer to the development of the world's first glucose-responsive insulin which, say researchers, will transform the treatment of diabetes.

The team has developed an innovative technology platform, which could be a key component to enable the next generation of insulin, able to react and adapt to glucose levels in the blood. This could eliminate the risk of hypoglycaemia - dangerously low blood sugar levels - leading to better metabolic control for people living with the disease. The science behind the research has been published in the journal Nature Chemistry.

The core structure is simple and symmetrical, yet provides a cavity which almost perfectly complements the all-equatorial β-pyranoside substrate. The receptor’s affinity for glucose, at K_a ~ 18,000 M⁻¹, compares well with natural receptor systems. Selectivities also reach biological levels. Most other saccharides are bound approximately 100 times more weakly, while non-carbohydrate substrates are ignored. 

"Indeed, our new molecule performs better than anyone would have thought possible. It binds glucose 100 times more strongly than any of our previous efforts and is almost perfectly selective for its target. It is fully comparable with the natural molecules that bind glucose, despite being many times smaller." the author says.

There are good prospects for using the synthetic receptor to help diabetics.

Firstly, it could be the key to developing glucose-responsive insulin - insulin which becomes inactive when glucose is not present. This could free diabetics from the fear of hypoglycemia, where glucose levels sink to dangerously low levels.

Secondly it could be used in continuous glucose monitors, which would allow diabetics to know their glucose levels at all times.

The author added: "On a scientific level, we have shown that small synthetic molecule can match the performance of evolved natural molecules (proteins), even when the task is unusually difficult (the selective binding of glucose in water has always been thought to be exceptionally challenging).

"After so many years trying, it is fantastic that we have made something that could save so many lives."

http://www.bristol.ac.uk/news/2018/november/glucose-binding-molecule-.html

https://www.nature.com/articles/s41557-018-0155-z