Capreomycin — A polypeptide antitubercular antibiotic with unusual binding properties toward copper(II)

Kamila Stokowa, Wojciech Szczepanik, Nicola Gaggelli, Elena Gaggelli, Gianni Valensin, Małgorzata Jeżowska-Bojczuk, Kamila Stokowa, Wojciech Szczepanik, Nicola Gaggelli, Elena Gaggelli, Gianni Valensin, Małgorzata Jeżowska-Bojczuk, Kamila Stokowa, Wojciech Szczepanik, Nicola Gaggelli, Elena Gaggelli, Gianni Valensin, Małgorzata Jeżowska-Bojczuk

Index: J. Inorg. Biochem. 106(1) , 111-6, (2012)

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Abstract

Capreomycin is an important therapeutic agent having intriguing and diverse molecular features. Its polypeptidic structure rich in nitrogen donors makes the drug a promising chelating agent for a number of transition metal ions, especially for copper(II). The results of the model investigational studies suggest that capreomycin anchors Cu 2+ ion with an amino function of the α,β-diaminopropionic acid residue at pH around 5. At physiological pH copper(II) ion is coordinated by two deprotonated amide nitrogen atoms of the α,β-diaminopropionic acid, the serine residue as well as the amino function deriving from the β-lysine. Above that pH value we observe a rearrangement within the coordination sphere leading to movement of Cu 2+ to the center of the peptide ring with concurrent coordination of four nitrogen donors. Spin–lattice relaxation enhancements and potentiometric measurements clearly indicate that deprotonated amide nitrogen atom from the β-ureidodehydroalanine moiety is the fourth donor atom.