Zinc binding with l-dopa peptides

• Published in: Inorganica Chimica Acta Vol. 461; pp. 120 - 126
• Main Authors: Veldkamp, Kelsey L., Tubergen, Philip J., Swartz, Mason A., DeVries, Jodie T., Tatko, Chad D.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-05-2017; Elsevier Science Ltd
• Subjects: Binding; Dihydroxyphenylalanine; Homeostasis; Mass spectrometry; NMR; Nuclear magnetic resonance; Pathology; Peptide binding; Peptide bound l-dopa; Peptides; Spectrophotometry; Studies; Tyrosine; Zinc; Zinc chelation; Zinc complexes; Zinc compounds; β-Hairpin peptide; β-Hairpin peptide; Peptide bound l-dopa; Zinc complexes; Peptide binding; Zinc chelation
• ISSN: 0020-1693; 1873-3255
• DOI: 10.1016/j.ica.2017.02.006

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•l-dopa is incorporated into a series of β-hairpin peptides.•The catechol of l-dopa is found to bind to zinc from spectroscopic, mass spectrometry and NMR investigations.•The binding stoichiometry of peptide and zinc is found to be 1:1 under the conditions examined.•Association energies range from 4.3 to 5.2kcalmol−1.
The combination of zinc dyshomoeostasis and oxidative damage has been linked to a number of human disease pathologies. A common pathway of oxidative damage centers on tyrosine with the generation of 3,4-dihydroxyphenylalanine (l-dopa). Once formed this catecholic moiety can be involved in metal binding. Herein, an l-dopa residue is incorporated into a peptide designed to adopt a β-hairpin configuration. Variation of the cross strand partner to l-dopa introduces an aromatic pair to enhance structure. Mass spectrometry indicates successful zinc binding, consistent with a 1:1 peptide:zinc complex. NMR and spectrophotometric investigations reveal the l-dopa as the binding locus with association energies ranging between 4.3 and 5.2kcalmol−1.