Interactions of disulfide-constrained cyclic tetrapeptides with Cu2+

Abstract

The purpose of this work is to characterize the interactions of two disulfide-constrained cyclic tetrapeptides [c(Ac-Cys-Pro-Phe-Cys-NH(2)), SS1; c(Ac-Cys-Pro-Gly-Cys-NH(2)), SS2] with Cu(2+) ions in order to facilitate the design of cyclic peptides as sensors for metal ions. The Cu(2+)-peptide complex cations at m/z 569.1315 for Cu(2+)-SS1 and m/z 479.0815 for Cu(2+)-SS2 were detected by mass spectrometry. The gas-phase fragmentation of the Cu(2+)-peptide complexes was studied by collision-induced dissociation and suggests the atoms involved in the coordination. Cu(2+) ion binds to a single SS1 or SS2 with K (d(app)) of 0.57 ± 0.02 and 0.55 ± 0.01 μM, respectively. Isothermal titration calorimetry data indicate both enthalpic and entropic contributions for the binding of Cu(2+) ion to SS1 and SS2. The characteristic wavenumber of 947 cm(-1) and the changes at 1,664 and 1,530 cm(-1) in the infrared spectrum suggest that the sulfydryl of cysteine, the carbonyl group, and amide II are involved in the coordination of Cu(2+). The X-ray absorption near-edge structure signal from the Cu(2+)-peptide complex corresponds to the four-coordination structure. The extended X-ray absorption fine structure and electron paramagnetic resonance results demonstrate the Cu(2+) ion is in an S/N/2O coordination environment, and is a distinct type II copper center. Theoretical calculations further demonstrate that Cu(2+) ion binds to SS1 or SS2 in a slightly distorted tetragonal geometry with an S/N/2O environment and the minimum potential energy.

Metal complexes of amino acids and peptides

“…It was shown that human amylin significantly decreases the amount of H 2 O 2 in solution produced by Cu(II) and glutathione. 298 Peptides of Cys are among the most powerful ligands of soft metal ions. 294 Oxytocin is a nonapeptide hormone with a disulfide bridge between Cys(1) and Cys (6) residues.…”

The effects of amino acid sequence and solvent polarity on the self-assembling of cyclic peptide nanotubes and molecular channel formation inside the lipid bilayer

“…Another interesting ability of the CPs is related to their application as the sensors for selective detection of different ions and compounds [27,28]. For example, Zhang and coworkers studied the sensing ability of cyclo-(Cys-Pro-Phe-Cys) and (Cys-Pro-Gly-Cys) for selective detection of Cu 2+ [29]. Theoretical calculations and spectroscopic analysis revealed that the CP composed of phenylalanine has greater sensitivity against Cu 2+ than CP having glycine amino acid.…”

Selective complexation of alkaline earth metal ions with nanotubular cyclopeptides: DFT theoretical study

“…The interaction of metal cations with cyclic peptides has been subjected of various studies especially for obtaining sequence information. [48][49][50][51][52][53][54][55][56][57][58] For example Williams and Brodbelt used low energy collisionally activated dissociation (CAD) in a quadrupole ion trap were used to characterize the fragmentation of alkali, alkaline earth and transition metal complexes of ve cyclic peptides. 48 Moreover, Zhang et al studied the interaction of disulde-constrained cyclic tetrapeptides with Cu 2+ .…”

“…48 Moreover, Zhang et al studied the interaction of disulde-constrained cyclic tetrapeptides with Cu 2+ . 57 In addition, Ruotolo and co-workers performed a conformational analysis of Gramicidin S, a cyclic antimicrobial peptide and found a b-sheet conformational preference. 52 Recently, we have investigated the ability of cyclo alanines with different sizes for separating lactic acid enantiomers and metal alkali cations.…”