Speciation of cyclo(Pro-Gly)₃ and its divalent metal-ion complexes by electrospray ionization mass spectrometry

Abstract

Electrospray ionization mass spectrometry (ESI-MS) was used to study the binding of selected group II and divalent transition-metal ions by cyclo(Pro-Gly) 3 (CPG3), a model ion carrier peptide. Metal salts (CatX n ) were combined with the peptide (M) at a molar ratio of 1:10 M/Cat in aqueous solvents containing 50% vol/vol acetonitrile or methanol and 1 or 10 mM ammonium acetate (NH 4 Ac). T he biogeochemistry of a particular metal ion is strongly influenced by its ability to form stable complexes with dissolved organic compounds under ambient conditions [1][2][3]. Identification and characterization of these complexes is critical to understanding and predicting the bioactivity and distribution of metals in biological systems and the environment. Peptides constitute one of the most important classes of compounds involved in the binding and transportation of metal ions [4,5]. Cysteine-containing peptides such as phytochelatins (PCs) and metallothioneins (MTs) have long been implicated in the binding, detoxification, and sequestration of heavy metals [5]. These compounds have been found in bacteria, plants, and animals, suggesting a universal role in metal detoxification and homeostasis. Alteration of MT expression and PC biosynthesis has been investigated as a means of increasing metal tolerance and uptake in plants, with the intention of using them for remediation of metalcontaminated sites [5][6][7][8]. However, this approach currently is limited by the low specificity with which metals such as cadmium, copper, and zinc bind to and induce expression of these peptides. Moreover, interactions between these metals and MTs or PCs in vivo remain poorly understood, while apparent localization of MT-metal complexes in roots limits uptake, translocation, and recovery of metals from aerial tissues [5,6].Biosynthesis and release of peptides and related compounds is another mechanism by which microorganisms such as soil bacteria and marine phytoplankton are able to regulate uptake of essential and nonessential metals from their surroundings [9,10]. Such compounds include cysteine-containing tripeptides similar to glutathione and PCs [11] and cyclic peptides such as rhodotorulic acid, a bacterial siderophore [12]. Many cyclic peptides have antibiotic or antifungal properties that arise from the ability to bind and transport metals across biological membranes [4,13,14]. These peptides show a high degree of specificity, forming stable complexes with metal ions of a particular charge and ionic radius. Metal binding specificity is related to the size and conformation of the peptide and the type and orientation of groups involved in metal binding [14]. It also is affected by solvent-metal and solvent-ligand interactions [4,14]. Biosynthesis of cyclic peptides in plants could, in principle, be used to promote uptake of specific metals, thereby enhancing the phytoremediative properties of metal (hyper)accumulators or the

Theoretical study of microhydrated cyclo(L-pro)4-alkali cation complexes

“…Many biological properties of cyclic peptides arise from the ability to bind and transport metals across biological membranes [8] and therefore the cyclic peptide-metal cation complexes constitute very attractive investigational field. Many experimental and theoretical studies have investigated the coordination chemistry of cyclic peptides [9][10][11][12][13][14].…”

Metal ion binding of s-block cations and nanotubular cyclic (proline)4: A theoretical study

“…Hioki et al [27] synthesized N-substituted cyclic triglycines and considered their response to various metal ions and demonstrated that N-substituted cyclic triglycines can act as host molecules. A theoretical study on the interaction of metal ions with cyclo[(1R,3S)-c-Acc-Gly] 3 hexapeptide shows its high affinity toward metal ions [35]. Several other studies have also considered the metal cation binding properties of cyclic peptides [36][37][38][39][40].…”

Metal‐Ion‐Mediated Supramolecular Assembly of C3‐Peptides

“…[19] The coordination ability of various metal ions to C 3 -peptides was further investigated,a nd two kinds of metal ions were added to aT HF solution of 1a successively to examine possible competition effects between different metal ions. [20] Protic solvents such as H 2 Oa nd MeOH diminished the tendency of these C 3 -peptides to form ordered supramolecular assemblies, presumably owing to strong hydrogen bondingb etween the solventand C 3 -peptides. However,w hen Ba 2 + ion was added to the solution of 1a with Zn 2 + ,N i 2 + , Mg 2 + or Cu 2 + ,t he pattern of the originalC Ds pectra was inverted, imitatings imilar spectra to that mediated solely by Ba 2 + (Figures 4d and S12).…”

“…CD spectra with an inverted pattern were also observed through addition of Ca 2 + or Sr 2 + to solutions of 1a with Zn 2 + ,N i 2 + ,M g 2 + or Cu 2 + .T hese resultsd emonstrate that coordinations of Ba 2 + ,C a 2 + and Sr 2 + with C 3 -peptides are much stronger than those of the other metal ions examined.T he chirality inversion may be ascribed to the fact that the geometries formed with Ba 2 + ,C a 2 + and Sr 2 + are dif-ferent from those with Zn 2 + ,N i 2 + ,M g 2 + and Cu 2 + ,w hich enables opposite-ordered packing modes. [20] Protic solvents such as H 2 Oa nd MeOH diminished the tendency of these C 3 -peptides to form ordered supramolecular assemblies, presumably owing to strong hydrogen bondingb etween the solventand C 3 -peptides. Addition of metal ions with strong coordinatione fficiency such as Ba 2 + cannotc ompensate for the dissolution caused by protic solvents, since no significant changes were observed in the CD spectra beforea nd after addition of metal ions ( Figure S13).…”