Interactions of disulfide-constrained cyclic tetrapeptides with Cu(2+)

Area of Science:

• Biochemistry
• Analytical Chemistry
• Materials Science

Background:

• Cyclic peptides offer potential for metal ion sensing.
• Understanding metal-peptide interactions is crucial for sensor development.

Purpose of the Study:

• To characterize the interactions between two disulfide-constrained cyclic tetrapeptides (SS1 and SS2) and Cu(2+) ions.
• To provide insights for designing cyclic peptides as effective metal ion sensors.

Main Methods:

• Mass spectrometry (MS) and collision-induced dissociation (CID) for complex detection and fragmentation.
• Isothermal titration calorimetry (ITC) to determine binding thermodynamics.
• Infrared (IR) spectroscopy, X-ray absorption spectroscopy (XAS), and electron paramagnetic resonance (EPR) for coordination environment analysis.
• Theoretical calculations to model binding geometry and energy.

Main Results:

• Cu(2+) ions bind to SS1 and SS2 with high affinity (K(d(app)) ~0.56 μM).
• Binding involves both enthalpic and entropic contributions.
• Spectroscopic and XAS data reveal a Cu(2+) coordination environment involving sulfur, nitrogen, and oxygen atoms (S/N/2O).
• Type II copper center formation and a distorted tetragonal geometry were identified.

Conclusions:

• The characterized Cu(2+)-peptide interactions provide a foundation for developing novel metal ion sensors.
• The coordination environment and binding thermodynamics offer critical parameters for sensor design and optimization.