Studies of the Gas-phase Acidity of D/L-Cysteine-Containing Polyalanine Peptides with Computational Chemistry and Mass Spectrometry
Poster Number
77
Faculty Mentor Name
Jianhua Ren
Research or Creativity Area
Natural Sciences
Abstract
D-amino acids have been found in nearly all living organics, including humans. However, the chemistry of the D-amino acids is largely unknown. Conversion of an amino acid from the L-form to the D-form often modifies the biological activity of the peptides, and in many cases, enhances their biological functions. Gas-phase acidity represents the intrinsic property of peptides containing ionizable amino acid residues. This study focused on characterization of several important parameters affecting the gas-phase acidity of oligopeptides consisting of one D/L-configuration cysteine residue and a polyalanine backbone.
The gas-phase acidities were determined using a tandem quadrupole mass spectrometer by applying the CID bracketing experiments and the extended kinetic method. The conformations and the energetics of model peptides were obtained computationally using a series of approaches. Conformational search was performed using the CREST program, which gives a pool of low-energy conformations. Subsequent geometry optimization and frequency calculations were carried out using the density functional theory at ωB97xD/6-311+G(d,p) level, which yields the final pool of lowest energy conformations. Theoretical gas-phase acidities were calculated based on Boltzmann averaged free energies of the final pool of conformations. Noncovalent interactions were examined using the reduced density gradient analysis.
Results
A library of tetrapeptides has been studied. Computational data and mass spectrometry results showed agreement to a large extent. In general, the gas-phase acidity decreases when the cysteine residue moves from the N- to the C-terminus. The D/L-configuration of the cysteine residue alters the conformations in subtle ways. Acetylation also appears to increase attractive noncovalent interactions for peptide ions, making acetylated peptides more acidic than non-acetylated analogs. Noncovalent interactions and helical dipole may have great influence on the gas-phase acidities of these model peptides.
Significance
This fundamental research will help scientists understand the unusual acidity of certain residues in proteins, which will further reveal the mechanism of some biochemical reactions and processes.
Location
University of the Pacific, DeRosa University Center
Start Date
26-4-2025 10:00 AM
End Date
26-4-2025 1:00 PM
Studies of the Gas-phase Acidity of D/L-Cysteine-Containing Polyalanine Peptides with Computational Chemistry and Mass Spectrometry
University of the Pacific, DeRosa University Center
D-amino acids have been found in nearly all living organics, including humans. However, the chemistry of the D-amino acids is largely unknown. Conversion of an amino acid from the L-form to the D-form often modifies the biological activity of the peptides, and in many cases, enhances their biological functions. Gas-phase acidity represents the intrinsic property of peptides containing ionizable amino acid residues. This study focused on characterization of several important parameters affecting the gas-phase acidity of oligopeptides consisting of one D/L-configuration cysteine residue and a polyalanine backbone.
The gas-phase acidities were determined using a tandem quadrupole mass spectrometer by applying the CID bracketing experiments and the extended kinetic method. The conformations and the energetics of model peptides were obtained computationally using a series of approaches. Conformational search was performed using the CREST program, which gives a pool of low-energy conformations. Subsequent geometry optimization and frequency calculations were carried out using the density functional theory at ωB97xD/6-311+G(d,p) level, which yields the final pool of lowest energy conformations. Theoretical gas-phase acidities were calculated based on Boltzmann averaged free energies of the final pool of conformations. Noncovalent interactions were examined using the reduced density gradient analysis.
