Mimicking Reverse Turns with Cyclic Tetrapeptides

Reverse turns are one of the most ubiquitous secondary structures in proteins. Created when the four amino acids in the main chain of a protein bends back on itself roughly 180 degrees, reverse turns are located largely on the exterior of globular macromolecules. Often involved in protein protein interactions reverse turns the pharmaceutical industry often aim to mimic them with small molecules. Historically reverse turns have been described by four torsions in the second and third residues of the turn. However, reverse turns are recognized by their side chains and not the peptide backbone, and it has recently been shown that the topology of the 4 Calpha-Cbeta bonds can more descriptively cluster turns

My thesis involved the conformational prediction (using insilico conformational searches) of cyclic tetrapeptides(CTPs) and screening them as possible turn mimetics. The entire Protein Data Bank (PDB) was screened against a CTP library i created which was found to able to mimic 54% of reverse turns in the PDB. These CTPs can act as lead compounds or therapeutics in their own right. See CV for publications.