Better drugs by evolution

Medicine often works by interacting with a specific protein in the body. This works much like a key (the active substance) that exactly fits the lock (the protein). By inserting the key into the lock, the function of the protein changes—it may be 'switched off' or become more active. 

'Small cyclic peptides' (SCPs) are promising compounds to be developed into medication, because they may fit locks that traditional drugs do not. In her research, Titial Oppewal developed a system for the synthesis and selection of suitable small cyclic peptides (SCPs) that can bind to chosen target proteins. 

For this purpose, she mimiced evolution in the laboratory. This process consists of three parts: First, a vast number of new SCP variants are randomly created. Each of these variants has a different sequence of amino acids and, therefore, a different three-dimensional shape. Additionally, a 'functional motif' is incorporated, which is not an amino acid but a different type of molecule that can enhance the pharmacological effect of the SCP. Next, the variants that bind to the target protein are selected. Finally, the nature of the matching SCP is determined, and more of the selected SCP is produced. In other words: countless keys are first created, each slightly different in shape; then, an efficient method is used to determine which keys fit the given lock best; finally, the matching keys are isolated, identified, and mass-produced.

Dissertation: https://hdl.handle.net/11370/949f8ed8-bb29-4906-b7ff-9632ee0e07bd