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Master thesis (Masterarbeit) in Organic Chemistry/Medicinal Chemistry
In this project, you will combine retrosynthesis of one of the hit molecules, design of modifications through 3D software visualization of the protein-hit complex and synthesis of the planned derivatives.
Keywords: retrosynthesis, medicinal chemistry, organic synthesis, epitranscriptomics, cancer
Epitranscriptomics gathers all RNA modifications, which do not alter the nucleotide sequence. Among these modifications, several of them are involved in gene expression and play a key role in diseases such as cancer. m6A is the most prevalent RNA modification (over 160 reported so far) and became the focus of extensive research in the past years.
Currently, the role of m6A in biological processes and particularly in diseases remain elusive. Therefore, the Caflisch group identified several hits of m6A interacting proteins, by
computer-based methods, in order to develop small molecules able to bind these proteins and unravel their role. One of these hits has been successfully optimized to a low nanomolar inhibitor with favorable ADMET properties. However, there are several other hits waiting for an enthusiastic organic synthesis student to start a medicinal chemistry hit-to-lead campaign. The 30 crystal structures of the m6A writer enzyme complexes solved in house will be used for protein
structure-based hit optimization.
In this project, you will combine retrosynthesis of one of the hit molecules, design of modifications through 3D software visualization of the protein-hit complex and synthesis of the planned derivatives. The aim is to obtain potency improvement while, as far as possible, consider ADMET properties to achieve a lead molecule. The different synthesized compounds will be evaluated in biochemical/biophysical assays and if relevant in cell based experiments.
Epitranscriptomics gathers all RNA modifications, which do not alter the nucleotide sequence. Among these modifications, several of them are involved in gene expression and play a key role in diseases such as cancer. m6A is the most prevalent RNA modification (over 160 reported so far) and became the focus of extensive research in the past years.
Currently, the role of m6A in biological processes and particularly in diseases remain elusive. Therefore, the Caflisch group identified several hits of m6A interacting proteins, by computer-based methods, in order to develop small molecules able to bind these proteins and unravel their role. One of these hits has been successfully optimized to a low nanomolar inhibitor with favorable ADMET properties. However, there are several other hits waiting for an enthusiastic organic synthesis student to start a medicinal chemistry hit-to-lead campaign. The 30 crystal structures of the m6A writer enzyme complexes solved in house will be used for protein structure-based hit optimization. In this project, you will combine retrosynthesis of one of the hit molecules, design of modifications through 3D software visualization of the protein-hit complex and synthesis of the planned derivatives. The aim is to obtain potency improvement while, as far as possible, consider ADMET properties to achieve a lead molecule. The different synthesized compounds will be evaluated in biochemical/biophysical assays and if relevant in cell based experiments.
The aim is to obtain potency improvement while, as far as possible, consider ADMET properties to achieve a lead molecule. The different synthesized compounds will be evaluated in biochemical/biophysical assays and if relevant in cell based experiments.
The aim is to obtain potency improvement while, as far as possible, consider ADMET properties to achieve a lead molecule. The different synthesized compounds will be evaluated in biochemical/biophysical assays and if relevant in cell based experiments.