¹H NMR studies of copper binding by histidine‐containing peptides

Abstract

We review recent developments in the studies of Cu(II) complexes with histidine-containing peptides in solution by NMR. An overview of the theoretical background of the effects of the paramagnetic metal on the NMR properties (relaxation and shift) of nearby nuclei is given. Particular attention is paid to the effect of exchange rates between free and metal-bound forms of the ligand on detection of paramagnetic relaxation rates. General methods are underlined to determine the structure of the complexes (and thus the donor set to the metal) and to distinguish between the binding of copper(II) to either N-1 or N-3 of the imidazole ring of histidine. Examples are reported dealing with fragments of the amyloid precursor protein (a protein related to Alzheimer's disease) and of the prion protein (related to Creutzfeldt-Jakob disease) in which the binding of copper may be relevant for subsequent redox activities, protein aggregation or metal-catalyzed protein damage.

1H and 13C NMR study of the complex formed by copper(II) with the nucleoside antibiotic sinefungin

“…The absence of direct scalar effects on neighbouring protons may indicate that an intervening Cu(II)-bound water molecule mediates such interaction(s). As a matter of fact, these two nitrogens are involved in copper binding of many adenosine-containing molecules (Jaworska et al, submitted manuscript, and [38][39][40][41][42] and their occurrence in the outer coordination sphere is not surprising.…”

“…(1) is needed whenever structural information on Cu(II) complexes is considered. As usually encountered with other copper(II) complexes [40][41][42], the residence life-time of the metal at its binding site makes a sizeable contribution to the paramagnetic relaxation rate which cannot be neglected. In such a situation the closer is a proton to the paramagnetic ion the faster is R 1b and, therefore, the more important becomes the contribution of exchange to R 1p .…”

The His–His sequence of the antimicrobial peptide demegen P-113 makes it very attractive ligand for Cu2+

“…In all the investigated systems the calculated R 1p values (Table 3) of the His He (He-Cu 2+ distance 0.31 nm) allowed the determination of s Im M reported in Table 3 [37][38][39][40][41]. For calculations the values of s c = 2.2 ± 0.3 ns (obtained from Stokes equation) and s e = 1-5 ns were used [42].…”

Copper Homeostasis and Neurodegenerative Disorders (Alzheimer's, Prion, and Parkinson's Diseases and Amyotrophic Lateral Sclerosis)

“…This apparent paradox can be explained by taking contributions of the exchange rate from the metal coordination sphere into account. 40,53 In solutions of ligands containing paramagnetic ions as cosolute, both the longitudinal (R 1obs ) and the transverse (R 2obs ) nuclear relaxation rates are averaged over the values of the free ligand molecules in the bulk (R 1f or R 2f ) and those of the ligand molecules residing in the metal coordination sphere and experiencing the effects of the electron spin magnetic moment (R 1b or R 2b ):…”