Quantifying transient interactions between amide groups and the guanidinium cation

Abstract

We study the interaction of the guanidinium cation, a widely used protein denaturant, with amide groups, the common structural motif of proteins. Our results provide evidence for direct contact between guanidinium and ∼2 amide groups, but the interaction is transient and weaker than for other cations with high charge-density.

Spezifische Ionen‐Effekte am Beispiel eines Oligopeptids: die Rolle zweizähniger Koordination beim Guanidinium‐Kation

“…These observed effects for KI, KSCN, and LiCl on GGG are in qualitative agreement with effects reported for these salts interacting with NMA. [14,15,17] For KCl, where the interaction with NMA was found negligible, [14,15,17] we find a minor reduction SGGG. Hence, the interaction of most salts with an isolated amide group in NMA is similar to the interaction with the two amide groups and the termini of GGG.…”

“…To this end, we use KCl, LiCl, guanidinium chloride (GdmCl), KI and KSCN to study how different anions and cations affect GGG. Comparison to our earlier studies [14,15,17,18] on how these salts affect the rotational mobility of a model amide, N-methylacetamide (NMA), and molecular dynamics (MD) simulations on GGG in the presence of KCl, KI, and GdmCl allows us assessing the contribution of the termini on ion-specific interaction strengths. The dielectric spectrum of an aqueous solution of triglycine at cGGG =0.3 mol·L −1 .…”

“…[10] Model systems such as amide-rich molecules have been often used to elucidate ionprotein interaction. [3,[11][12][13][14][15][16][17][18] These amide models, however, lack charged residues (e.g., the C-and N-termini) that are intrinsically sensitive to electrostatic interaction with…”

“…[19] Hence, these studies [12,19] have providedpredominantly nuclear magnetic resonance (NMR) spectroscopic and computational -evidence for the termini being crucial when considering the anion-protein interaction. While cation-amide interactions have been shown to be significant, [11,[14][15][16] the effect of cations on oligopeptides and thus the effect of charged termini on interactions of model molecules with cations has been little explored. [20,21] In the present work, we study the effect of both cations and anions on the oligopeptide triglycine (GGG), which contains both (two) amide groups and charged termini (-COOand -NH3 + ).…”

“…This increase in GGG with increasing csalt is in line with our earlier findings for NMA and can be related to an increase in the samples viscosity with increasing csalt. [14] Conversely, the amplitude of the GGG relaxation SGGG decreases upon addition of salts. While KCl shows a moderate decrease, salts containing anions with a stronger tendency to denature proteins (KI and KSCN) have a more pronounced effect on SGGG.…”