Capping Motif for Peptide Helix Formation.

Area of Science:

• Biophysical Chemistry
• Computational Chemistry
• Peptide Science

Background:

• C-terminal lysine is known to stabilize helix formation in polyalanine peptides of seven or more residues.
• The structural role of lysine in shorter peptides remains less understood.

Purpose of the Study:

• To investigate the helix-stabilizing role of C-terminal lysine in short peptides.
• To characterize the structural motif formed by lysine in peptides using experimental and computational methods.

Main Methods:

• Cold ion spectroscopy to probe peptide structures in the gas phase.
• Density Functional Theory (DFT) calculations to model peptide conformations and interactions.
• Analysis of vibrational frequencies of amide N-H stretches.

Main Results:

• A three-residue peptide (Ac-Phe-Ala-LysH(+)) adopts a structure where lysine forms three hydrogen bonds with backbone carbonyls, mimicking helix capping.
• This lysine-mediated capping motif was confirmed in longer peptides (Ac-Phe-(Ala)5-LysH(+) and Ac-Phe-(Ala)10-LysH(+)).
• Spectroscopic analysis identified characteristic N- and C-terminal amide N-H stretches above 3400 cm(-1) (unpaired) and helical core stretches below 3400 cm(-1).

Conclusions:

• C-terminal lysine can stabilize helix formation even in very short peptides by forming a specific capping motif.
• This motif is conserved across different peptide lengths, highlighting its generality.
• Spectroscopic signatures of N- and C-terminal amide N-H bonds provide insights into peptide secondary structure.