| alpha-/beta-amino acids are the constituent units of peptides and proteins, as well as important starting materials for the synthesis of pharmaceutically important intermediates and drugs. In the present study, the first set of reliable experimental K+ affinities of the twenty naturally occurring ctamino acids were determined using the mass spectrometric kinetic methods and estimated theoretically using the density functional theory (DFT) B3-LYP/6-311+G(3df,p)//B3-LYP/6-31G(d) protocol. The most stable K + binding mode of Ser, Thr, Cys, Met, Phe, Tyr, Trp, Asp, and Asn involves a tridentate binding to the backbone O=C, N-terminal NH2, and the O/N-heteroatom sites in the charge-solvated CS2 form, while the zwitterionic ZW1 form is found to be most stable for the K+-Pro/Glu/Gln/Lys/His/Arg complexes.;The most stable proton (H+) binding site of five biologically important beta-amino acids and four model beta-dipeptides is at the N-terminal amino nitrogen (NH2), while K+ binds to the two carboxylic oxygens [O=C and --OM of the beta-amino acids in the most stable charge-solvated CS1 mode. For carnosine ((beta-Ala)His), the most stable proton binding site is at the pi-nitrogen of the imidazole ring of the histidine residue. The enhanced proton (H+) affinities (PA) of the beta-amino acids and beta-dipeptides are attributed to a more stabilizing hydrogen bond or bonding network with much more pronounced effects when beta-Ala is located at the N-terminus than at the C-terminus of the beta-dipeptides.;The potential energy surfaces for the dissociation of protonated beta-alanine (beta-Ala), two model beta-dipeptides. (beta-Ala)Gly and Gly(beta-Ala), and two histidine-containing model dipeptides, GlyHis and [HisGly, including the reaction intermediates, transition structures (energy barriers) and energetics of the reaction (DeltaH0, DeltaH298, and DeltaG 298) were found using the DFT protocol. For protonated beta-Ala, characteristic loss of H2O, CH2CO, and (CH2CO + H2 O) pathways, are found to be energetically preferred. The formation of the b2(oxazolone-His) ions from [GlyHis + H)+ and [HisGly + H]+ are found to be energetically and entropically favoured, but b2(diketopiperazine-His) and b2(bicyclic) ions could also be formed at higher critical energies. However, given sufficient internal energy imarted by collisional activation, initially formed b 2(oxazolone-His) ions could further isomerize to the more stable cyclic b2(diketopiperazine-His) ions, thereby losing the sequence information provided by the b2 ions. The knowledge gained in the present study will he useful in sequence analysis of beta-peptides and histidine-containing peptides by tandem mass spectrometry. |
