Publication

Generation of photoswitchable peptide ligands by phage display

Silvia Bellotto
2015
EPFL thesis
Abstract

Photoswitchable ligands are used to control and study complex biological systems such as folding of proteins and peptides, enzymatic reactions or neuronal signaling. They are typically developed by conjugating photochromic compounds to known ligands so that exposure to light results in the change of the binding affinity of the ligand. Many light-responsive ligands are based on azobenzene, a molecule that undergoes a pronounced change in geometry upon photoisomerization from trans to cis in picoseconds. Currently, photoswitchable ligands are available only to a limited number of targets and their development by rational design is complex. Furthermore, they show low affinity and a relatively small change in binding affinity between the cis and trans conformation. In my PhD work, I aimed at overcoming these shortcomings by establishing an in vitro evolution method to generate light-controlled peptide ligands to targets of choice. Combining the expertise on phage display technology of the Heinis' lab and the knowledge about azobenzene photoswitches of the Wegner's lab, I screened large combinatorial libraries of cyclic peptides containing an azobenzene-based linker for the generation of light controlled ligands. [...]

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Related concepts (34)
Cell signaling
In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellular life in prokaryotes and eukaryotes. Signals that originate from outside a cell (or extracellular signals) can be physical agents like mechanical pressure, voltage, temperature, light, or chemical signals (e.g., small molecules, peptides, or gas).
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from Latin ligare, which means 'to bind'. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein. The binding typically results in a change of conformational isomerism (conformation) of the target protein. In DNA-ligand binding studies, the ligand can be a small molecule, ion, or protein which binds to the DNA double helix.
Signal transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events. Most commonly, protein phosphorylation is catalyzed by protein kinases, ultimately resulting in a cellular response. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used. The changes elicited by ligand binding (or signal sensing) in a receptor give rise to a biochemical cascade, which is a chain of biochemical events known as a signaling pathway.
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