Quantum chemical analysis of the unfolding of a penta-glycyl 3 _(10)-helix initiated by HO~?, HO_2~?, and O_2~(-?)

摘要

In this study, the thermodynamic functions of hydrogen abstraction from the C and amide nitrogen of Gly~3 in a homo-pentapeptide (N-Ac-GGGGG-NH_2; G5) by HO~?, HO_2~?, and O_2~(-?) were computed using the Becke three-parameter Lee-Yang-Parr (B3LYP) density functional. The thermodynamic functions, standard enthalpy (H), Gibbs free energy (G), and entropy (S), of these reactions were computed with G5 in the 3 _(10)-helical (G5_(Hel)) and fully-extended (G5_(Ext)) conformations at the B3LYP6-31G(d) and B3LYP6-311G(d,p) levels of theory, both in the gas phase and using the conductor-like polarizable continuum model implicit water model. H abstraction is more favorable at the C than at the amide nitrogen. The secondary structure of G5 affects the bond dissociation energy of the H-C, but has a negligible effect on the dissociation energy of the H-N bond. The HO~? radical is the strongest hydrogen abstractor, followed by HO_2~?, and finally O_2~(-?). The secondary structure elements, such as H-bonds in the 310-helix, protect the peptide from radical attack by disabling the potential electron delocalization at the C, which is possible when G5 is in the extended conformation. The unfolding of the peptide radicals is more favorable than the unfolding of G5_(Hel); however, only the HO~? can initiate the unfolding of G5_(Hel) and the formation of G5 _(Ext)~+. These results are relevant to peptides that are prone to undergoing transitions from helical structures to -sheets in the cellular condition known as oxidative stress and the results are discussed in this context.