Stereocontrolled synthesis and characterization of novel sugar-phosphate modified nucleotides

Promovendus/a: Marlies Derden

Promotor(en): Prof. dr. Eveline Lescrinier, Mevrouw Elisabetta Groaz

Over billions of years, nature has optimized DNA and RNA into remarkably efficient molecules that store and process genetic information. Although their basic chemical structure is relatively simple, they can perform extremely complex functions that make life possible. Scientists can expand the capabilities of these natural molecules by modifying their chemical structure, creating new types of genetic materials with properties that do not exist in nature. These artificial nucleic acids are increasingly important for applications in medicine and biotechnology.

In this thesis, we explore new forms of modified nucleic acids in which parts of the molecular backbone are deliberately altered. These modifications introduce a form of molecular “chirality,” meaning that the molecules can exist in different, non-identical mirror-image forms. This subtle difference can have a major impact on how the molecules behave, how they fold, and how they interact with biological systems.

A key challenge in this field is that making such modified nucleic acids in a controlled and reliable way is often very difficult, and there is still limited understanding of how their three-dimensional structure affects their function. To address this, this thesis develops new chemical methods that allow the precise preparation of these chiral building blocks in a single, well-defined form. Using these tools, we then study how the molecular structure of these artificial nucleic acids influences their properties and performance.

As such, this work ultimately contributes to the development of new genetic materials that may support future advances in biotechnology and medical research.