Luminescent Pt(II) tag for monitoring peptide (mis)folding and aggregation processes

• Applicant: Dr. Charles Lochenie
• Subject Area: Inorganic Molecular Chemistry - Synthesis and Characterisation ; Biochemistry ; Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2017 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 393103351

Today, it is very clear that the function or properties of a definite material does not always come from its single components, but also from the supramolecular arrangement of the molecules in space, time, and energy, and that is in solution, as well as in the solid state. In some cases, molecules spontaneously arrange in an organized supramolecular entity, the phenomenon being known as self-assembly. This process is essential to life, as it happens when a DNA double-strand forms through pair-matching, when peptides self-assembles into a protein, or when a cell membrane is built by phospholipids. In all cases, intermolecular interactions such as H-bonding, van der Waals interactions, or pi-interactions are the underlying driving force for the assembly.As just mentioned before, a peptide needs to be folded in order to achieve its function, however, for some peptides, misfolding and/or self-assembly can happen and lead to so-called amyloidosis, where misfolded polypeptides self-assemble into oligomeric b-sheets (protofibrils), which then aggregate into fibrils. The most well-known amyloidosis leads to Alzheimer’s disease, but Parkinson’s disease, diabetes type II, and prion diseases also belong to this class of illnesses, in each case a different protein is responsible for the building of the fibrils.However, observing the aggregation and disaggregation of amyloid peptides in living media, would require a reporter allowing monitoring in real time the formation of the fibrils, and differentiating between the aggregated and non-aggregated state. In this respect, Pt(II) luminescent complexes could be used as tag. With their emission in the visible region with a large Stokes shift, their high quantum yields, long excited state lifetimes, and high stability, Pt(II) complexes are ideal to be used as bio-imaging label. The research objective of this proposal is to design a luminescent tag for monitoring the aggregation processes of amyloid-like peptides. The novelty of this project lies in the fact that the designed luminescent Pt(II) tag would change its emission properties upon aggregation. The Pt(II) complex will be coupled on the N-terminal amino-acid of the peptides, and the photophysical properties as well as self-assembly behaviour of the new [Pt]-Peptide molecules will be studied. It is expected that upon aggregation, the Pt(II) complexes located at the end of the peptides will interact. As reported in literature, stacked Pt(II) complexes exhibit a different emission spectrum, which allow then the identification of aggregated peptides.

• DFG Programme: Research Fellowships
• International Connection: France
• Host: Professorin Dr. Luisa De Cola