PhD Defence Andreas Nilsson

Abstract:

Cyclodextrins (CDs) are water-soluble, non-toxic cyclic carbohydrates composed of glucose units linked together in a ring. CDs are produced on a ton-scale annually, as their ability to encapsulate small molecules is useful in the pharmaceutical, agricultural, and cosmetic industries. Many commercial pharmaceuticals on the market today contain cyclodextrins, and they are being studied for applications such as drug delivery and PFAS removal from water, among others. However, readily accessible cyclodextrins are limited in variety, as it is very difficult for chemists to produce selectively modified cyclodextrins due to the similar reactivity of functionalisable groups on the cyclodextrin.

This PhD thesis demonstrates a dynamic dual-enzyme approach to the production of modified cyclodextrins. First, the enzyme phosphorylase transfers functionalised glucose-1-phosphates to linear glucose chains. Then, the second enzyme, cyclodextrin glucanotransferase, can cyclise the linear glucose chains into CDs, as shown in the figure above.

This approach was shown to successfully introduce five different modifications into CDs. The formation of linear glucose chains and CDs is dynamic, meaning that the products constantly interconvert. This property was exploited to direct the system towards desired products, for example, by adding templates to enable the selective synthesis of CDs of specific sizes.

Cleavable cyclodextrins containing “trigger groups” were also synthesised. These trigger groups respond to external stimuli, such as light irradiation, which leads to the opening of the CD, turning it into a linear glucose chain. These CDs could be useful for drug delivery applications, as it was shown that a small molecule encapsulated within the cyclodextrin was released on demand by simply shining light on it.

Overall, this thesis adds another tool to the toolbox in the field of cyclodextrin chemistry, introducing a promising alternative to the conventional, lengthy stepwise chemical synthesis of modified CDs.

Principal Supervisor: 

Professor Sophie Beeren, DTU Chemistry

Co-supervisor: 
Professor Sebastian Meier, DTU Chemistry

Examiners:
Professor Robert Madsen, DTU Chemistry
Dr. Sébastien Ulrich, University de Montpellier
Professor Jan O. Jeppesen, University of Southern Denmark

Chairperson:
Senior Researcher Dennis Larsen, DTU Chemistry