DC15: Establishing a toolbox of warheads for covalent targeting of RNA

PhD project description:

The PhD project will focus on the design, synthesis, and characterization of covalent warheads targeting the 2’OH group in RNA nucleotides to create a broad toolbox to enable the discovery of covalent RNA ligands. Binding parameters will be optimized for both reversible and irreversible covalent binders, including time bound within the RNA, by tuning both steric and electronic properties of the warheads. Synthetic modification of warheads and synthesis of analogues will be essential to drive the discovery forward. The flavin mononucleotide (FMN) riboswitch will be used as model system for validating the warheads. Promising warheads will be appended onto the scaffold of known FMN riboswitch ligands to obtain covalently binding FMN ligands.

You will be responsible for the screening of commercially available candidate warheads and characterization of stability and identity of their adducts. Utilizing identified warheads, you will take part in the design of novel target compounds for synthesis and will be responsible for the development of synthesis routes, and synthesis of the target compounds. You will be tasked with developing new synthesis routes and using these to produce compound libraries for the purpose of establishing structure-activity relationships.

You will work in a team together with other synthesis- and medicinal chemists both within the TargetRNA doctoral network and the research group. The work tasks will be varied, and you will be given the opportunity to contribute to developing new solution in a research environment that focuses on innovation. Testing in biochemical assays will be carried out by other project members as well as external partners.

You are expected to co-supervise MSc-students and participate actively in professional activities within the TargetRNA network, the research group and at the Department of Chemistry.