Inducing α-Helicity in Peptides by Silver Coordination to Cysteine

Abstract

Short peptide sequences consisting of two cysteine residues separated by three other amino acids display complete change from random coil to α-helical secondary structure in response to addition of Ag⁺ ions. The folded CXXXC/Ag⁺ complex involves formation of multinuclear Ag⁺ species and is stable in a wide pH range from below 3 to above 8. The complex is stable through reversed-phase HPLC separation as well as towards a physiological level of chloride ions, based on far-UV circular dichroism spectroscopy. In electrospray MS under acidic conditions a peptide dimer with four Ag⁺ ions bound was observed, and modelling based on potentiometric experiments supported this to be the dominating complex at neutral pH together with a peptide dimer with 3 Ag⁺ and one proton at lower pH. The complex was demonstrated to work as a N-terminal nucleation site for inducing α-helicity into longer peptides. This type of silver-mediated peptide assembly and folding may be of more general use for stabilizing not only peptide folding but also for controlling oligomerization even under acidic conditions.

Keywords: cysteine; oligomerization; peptide; silver; α-helix.