Improving Bicyclic Peptide Phage Display and Development of Sortase A Inhibitors
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Proteins control nearly every facet of life on a molecular level. Proteins are formed from linear strings of amino acids, which fold into three-dimensional structures that can enact functions. Evolution has created highly efficient proteins in diverse fold ...
Sortases are transpeptidase enzymes that anchor surface proteins, including virulence factors, to the cell wall of Gram-positive bacteria, and they are potential targets for the development of anti-infective agents. While several large compound libraries w ...
The research described within this thesis is primarily motivated by two fields of science with reversed, yet complementary, approaches to addressing the same essential objective: manipulating and understanding the complex program of life. Whereas synthetic ...
Gene regulatory networks (GRNs) determine cellular behaviour, and ultimately the functioning of single- and multicellular organisms. Transcription factors regulate gene expression by binding to DNA or via remodelling chromatin. Recent advances in biotechno ...
Cyclic peptides can bind to protein targets with high affinities and selectivities, which makes them an attractive modality for the development of research reagents and therapeutics. Additional properties, including low inherent toxicity, efficient chemica ...
Cyclic peptide ligands are a promising molecular format for the development of therapeutics. They combine some of the advantages of large protein therapeutics (high affinity and specificity) and of small molecule drugs (accessibility to chemical synthesis ...
Bicyclic peptides are an attractive molecule format for the development of therapeutics and research tools. Our laboratory is specialized on the development of bicyclic peptide ligands by phage display. In brief, libraries of randompeptides each containing ...
High-throughput sequencing was previously applied to phage-selected peptides in order to gain insight into the abundance and diversity of isolated peptides. Herein we developed a procedure to efficiently compare the sequences of large numbers of phage-sele ...
Notch signaling is a highly conserved developmental pathway that plays important roles in the regulation of cellular processes including cell fate decisions and stem cell maintenance. A tight regulation of the Notch cascade ensures proper tissue homeostasi ...
Phage display relies on a bacterial infection step in which the phage particles are replicated to perform multiple affinity selection rounds and to enable the identification of isolated clones by DNA sequencing. While this process is efficient for wild-typ ...
