Tailoring the volatility and stability of oligopeptides

Area of Science:

• Analytical Chemistry
• Physical Chemistry
• Biochemistry

Background:

• Amino acids are fundamental biological molecules, with fluorinated derivatives showing promise in chemistry and medicine.
• Mass spectrometry allows gas-phase study of peptides, but typically as charged ions.
• Preparing thermally slow molecular beams of neutral peptides is crucial for advanced spectroscopic and interferometric techniques but is hindered by peptide bond fragility.

Purpose of the Study:

• To investigate perfluoroalkyl functionalization as a strategy to increase peptide volatility.
• To compare the effectiveness of perfluoroalkyl functionalization with other modifications like methylation, acylation, and amidation.
• To enable the formation of thermally slow molecular beams of intact neutral peptides.

Main Methods:

• Laser desorption of peptides into supersonic noble gas jets.
• Tailored perfluoroalkyl functionalization of peptides.
• Comparison of volatility and beam formation for functionalized peptides versus unmodified peptides.

Main Results:

• Perfluoroalkyl functionalization significantly reduces intermolecular binding, increasing peptide volatility.
• Intact neutral tripeptides were successfully prepared as thermal beams.
• Extensively fluoroalkyl-decorated nonapeptides yielded only fragments, indicating size limitations.

Conclusions:

• Perfluoroalkyl functionalization is an effective strategy for preparing volatile peptides suitable for slow molecular beam applications.
• This approach overcomes the limitations of peptide bond fragility and thermal denaturation.
• The findings pave the way for advanced spectroscopic and interferometric studies of peptides in the gas phase.