Addressing diabetes: Glucose recognition with a bespoke molecular glove

Dr Keith Andrews
Research Fellow 2019

Dr Keith Andrews
University of Oxford

Enzymes are molecular machines capable of detecting and modifying chemicals. Although humans have learned to hijack these machines (biological washing powder, DNA decoding, cheese-making!) and even edit them, building bespoke molecular machines with new functionality from scratch is still in its infancy. Learning to mimic enzymes efficiently would be a major breakthrough across science and engineering, with impact similar to production-line robotics. The reason enzymes are so effective is specificity; as with a machine on a production line, a given enzyme might perform only one function, but do so near perfectly. Although chemists are becoming adept general manipulators of matter, we remain near powerless to select a complex molecule and alter it directly at a specific atom.

There are countless molecules that we are still novices in editing and detecting that are vital to human prosperity – amino acids, sugars, the nucleobases of DNA. It is time chemists tackled the specific, and invented the chemical production-line from the bottom-up. In order to edit molecules with precision, we first need to recognise them. This proposal sets forward the development of a ‘molecular glove’ that can be tuned to recognise a single substrate molecule – just like an enzyme. 

“The invention of a molecular glove for glucose will provide a blueprint for recognising other important molecules”

First, a glucose molecule will be positioned within a molecular box, or nanocage. Further molecules will be added to the nanocage to fit around the glucose, much like a bespoke tailor stitching a glove around a hand. Removal of the hand – the glucose template – leaves a bespoke molecular glove able to detect glucose molecules, an essential technology for improving modern diabetes treatments.

The invention of a molecular glove for glucose will provide a blueprint for recognising other important molecules. This, then, would be the basis of a molecular production line. Even more importantly, it would pave the way for ‘enzymatic catalysis’ – once captured in the glove, each ‘finger’ of the molecule is amenable to precise atomic level changes. This will allow chemists to alter molecules in ways they have been unable to achieve with standard chemistry, bringing new blood to the sustainable chemical industries of the future.