Gas-phase Acidity of D/L-Cysteine-Containing Oligopeptides by Computational Study
Poster Number
21C
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 focuses on characterization of several important parameters affecting the gas-phase acidity of oligopeptides consisting of D/L-cysteine residues and polyalanine backbone. Incorporating just a single D-cysteine in an oligopeptide could alter the conformation and the gas-phase acidity.
Purpose
The purpose of this study is to systematically investigate the gas-phase acidities of cysteine-containing polyalanines using computational and experimental methods.
Results
For tetrapeptides with one cysteine (C) residue and three alanine (A) residues, the gas-phase acidities calculated at the ωB97xD /6-311+G(d,p) level showed similar trends as those obtained from mass spectrometry measurements. The Gibbs free energy change (ΔG) and enthalpy change (ΔH) of the deprotonation reaction were used to quantify the gas-phase acidity. The experimental values of ΔH were obtained to be 319.5, 320.3, 329.2, and 329.3 kcal/mol for CAAA, dCAAA, AAAC and AAAdC, respectively. The Computed values were 320.4, 321.9, 327.8, 329.3 kcal/mol for those tetrapeptides, which are very close to the experimental results. For N-acetylated tetrapeptides, the results were 322.4, 322.3, 325.8, 328.8 kcal/mol for Ac-CAAA, Ac-dCAAA, Ac-AAAC and Ac-AAAdC, making them slightly more acidic than their corresponding non-acetylated analogues.
In general, the gas-phase acidity decreases when the cysteine residue moves from the N- to the C-terminus. Charged peptides appear to be more compact if the cysteine residue is on the N- or the C-terminus. Charged peptides adopt more extended conformations when the cysteine residue is in the middle of the chain. RDG analysis shows that noncovalent interactions, especially hydrogen bonding, contribute significantly to the conformational stability of the peptide anions. The D/L-configuration of the cysteine residue alters the conformations in subtle ways. N-terminal acetylation enhances the gas-phase acidity. However, the effect appears to be greater for peptides containing a D-cysteine residue. Acetylation also appears to increase attractive noncovalent interactions for all peptide ions, which is consistent with the acidity enhancement.
Significance
Lots of enzyme active sites have cysteine residues and the acidity of these cysteine residues play an important role in enzyme activity. Our model peptides can mimic those active sites and help us study the nature of complex peptides. Our fundamental study can be further extended to biochemical and biological systems.
Location
Don and Karen DeRosa University Center (DUC) Poster Hall
Start Date
27-4-2024 10:30 AM
End Date
27-4-2024 12:30 PM
Gas-phase Acidity of D/L-Cysteine-Containing Oligopeptides by Computational Study
Don and Karen DeRosa University Center (DUC) Poster Hall
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 focuses on characterization of several important parameters affecting the gas-phase acidity of oligopeptides consisting of D/L-cysteine residues and polyalanine backbone. Incorporating just a single D-cysteine in an oligopeptide could alter the conformation and the gas-phase acidity.
