Copper(II) coordination properties of the integrin ligand sequence PHSRN and its new β-cyclodextrin conjugates

The peptide sequence PHSRN is the second cell binding site of the human fibronectin protein, a glycoprotein which plays a critical adhesive role during development, tissue repair and angiogenesis. The copper(II) complexes with the peptide fragment PHSRN were characterized by potentiometric and UV–visible, CD, EPR spectroscopic methods. Thermodynamic and spectroscopic evidences indicate that at physiological pH, only one copper(II) complex species, [CuLH−2], is present and the metal ion is bound to one imidazole and two amide nitrogen atoms (NIm, 2N−) in a tetrahedral distorted square planar coordination. Two new β-cyclodextrin–ethylendiamino derivatives with the PHSRN covalently attached were synthesized as multitargeting molecules, able to have a site-specific recognition sequence, to interact with copper(II) ions and to be a potential carrier of hydrophobic drugs. Copper(II) complexes with these β-cyclodextrin derivatives were characterized by means of potentiometric and spectroscopic techniques. The comparison of the experimental parameters determined at different pH values with those obtained for the parent peptide complex species, shows that at physiological pH the ethylendiamino-β-CD moiety does not influence the peptide interaction with copper ions and the β-CD hydrophobic cavity is not blocked, being available to host hydrophobic drugs such as naproxen. Copper(II) coordination environment of fibronectin peptide fragment PHSRN is not influenced at physiological pH, by its covalently binding to β-cyclodextrin-ethylendiamino moiety. [Display omitted] ► Copper(II) interaction with the PHSRN peptide has been characterized ► New b-cyclodextrin-PHSRN derivatives have been synthesized. ► At physiological pH, the b-CD component does not affect the peptide interaction with copper(II).