Molecular sensitised probe for amino acid recognition within peptide sequences

Area of Science:

• Surface Science and Nanotechnology
• Biophysical Chemistry
• Molecular Spectroscopy

Background:

• Investigating large biomolecules at the nanoscale typically uses low-temperature scanning tunnelling microscopy (LT-STM) combined with mass-selective electro-spray ion-beam deposition.
• Chemical identification of biopolymer building blocks is challenging due to complex structures, conformational flexibility, and often requires markers or simulations.

Purpose of the Study:

• To present a novel molecular probe-sensitisation approach for the specific chemical identification of amino acids within peptides.
• To enable nanoscale spectroscopic imaging and mapping of individual amino acid residues in biopolymers.

Main Methods:

• Utilised a molecular probe attached to the tip-apex of an LT-STM.
• Employed a sensitisation strategy where the probe selectively interacts with target amino acids on the peptide surface.
• Performed density functional theory (DFT) calculations to elucidate the interaction mechanism.

Main Results:

• Demonstrated that selective intermolecular interactions induce an enhanced tunnelling conductance at a specific spectral feature.
• Showcased the ability to map this enhanced conductance, enabling localisation of the target amino acid.
• DFT calculations suggest the mechanism involves sensitiser conformational changes and local charge redistributions, lowering the tunnelling barrier.

Conclusions:

• The molecular probe-sensitisation approach provides a pathway for direct chemical identification of amino acids in peptides at the nanoscale.
• This method overcomes limitations of existing techniques by enabling marker-free identification through enhanced spectroscopic signals.
• The findings pave the way for advanced characterisation of biomolecular structure and function at unprecedented resolution.