FELIX researchers create and characterize large neutral peptide aggregates

The organized clustering of peptides, or peptide aggregation, is related to neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Therefore it is widely studied. Until now, researchers could only use small, charged peptide clusters due to experimental limitations. FELIX researchers demonstrate for the first time that it is possible to create and characterize large aggregates of neutral peptides. This makes complementary studies on neutral biologically interesting peptides possible.

To understand the way peptides organize themselves and what exactly happens when peptides aggregate, we need to know more about its structure and structural changes during formation.
Ample methods have been developed to acquire structural information on the final stage, the so-called amyloid fibrils and plaques. But only a hand full of experiments study the lowly populated species on the pathway to form these fibrils.

Experiments limited

Currently, this structural characterization of aggregates and their mechanism of formation are done on charged species. Experiments on neutral aggregates would complement these studies. However, due to experimental limitations, the formation of aggregates of neutral molecules is not straightforward and up till now no peptide clusters were reported larger than two monomeric peptides (dimers).

Large, neutral peptide clusters

In this study, FELIX researchers Sjors Bakels, Sebastiaan Porskamp and Anouk Rijs adjusted the way the molecules are brought into the gas phase using laser desorption. By doing so, they were able to make large aggregates of up to even fourteen peptides. They have showed that they can select each aggregate by size and subsequently characterize its structure using mass- and conformer selective IR action spectroscopy and high-level quantum chemical calculations. They could also visualize the competition between intra- and intermolecular hydrogen bond interactions upon aggregate formation. The results pave the way to complementary studies on neutral biologically interesting peptides such as the hydrophobic amyloidogenic peptides.

Large neutral peptide aggregates were created using laser desorption and structurally assigned using infrared action spectroscopy.

Reference

Sjors Bakels, Sebastiaan B.A. Porskamp and Anouk M. Rijs, Formation of neutral peptide aggregates studied by mass selective IR action spectroscopy,Angew. Chem. Int. Ed, 2019

More information

Anouk M. Rijs