Proton and Metal Ion Interactions with Glycylglycylhistamine, a Serum Albumin Mimicking Pseudopeptide

Abstract

The macro- and microprotonations of glycylglycylhistamine (GGHA) have been determined by combined potentiometric and 1H-NMR methods. The complexation of GGHA with Co(II), Ni(II), and Cu(II) has been studied by potentiometric, EPR, and 1H-NMR methods. In the pH range 3−11.2, more or less deprotonated monomeric complexes (MLH, ML, MLH- 1, MLH- 2, MLH- 3) formed in all systems. In the case of Ni(II) and Cu(II) at physiological pH, the MLH- 2 species is predominant with four nitrogen coordination sites (one amino, two peptide, and one imidazole-N3 nitrogens) in square planar arrangement. In Co(II) containing systems however, CoL is the predominant complex near pH 7 with a macrochelate coordination of terminal amino and imidazole nitrogens, while CoLH- 2 species forms at much higher pH. In accordance with NMR measurements, the formation of MLH- 3 species can be assigned to the further deprotonation of the N1-pyrrolic nitrogen in the imidazole ring without metal coordination. The formation constants determined were compared with those of the analogous histidine derivatives. Single-crystal X-ray analysis of CuLH- 2·3H2O verified the expected four nitrogen coordination in the equatorial plane of Cu(II).

Tuning the coordination properties of multi-histidine peptides by using a tripodal scaffold: solution chemical study and catechol oxidase mimicking

“…Linear peptides have long since been used to mimic the metal binding sites of metalloproteins [1][2][3][4][5][6][7] and metalloenzymes. [8][9][10][11][12] Previously, we also studied some histidine-rich peptides in order to create similar metal ion environment to native enzymes.…”

“…[8][9][10][11][12] Previously, we also studied some histidine-rich peptides in order to create similar metal ion environment to native enzymes. 1,6,[8][9][10][11] Such metallopeptides may possess notable catalytic activity to promote either hydrolytic 8,14 or redox [9][10][11][12][13] reactions. However, from structural point of view, linear peptides may only be useful to mimic metal binding sites of native enzymes, if the residues involved in the coordination are part of a relatively short sequence.…”

A minimalist chemical model of matrix metalloproteinases — Can small peptides mimic the more rigid metal binding sites of proteins?

“…Such metal binding sites are obviously difficult to mimic by small peptides. However, a number of proteins possess relatively short histidine-rich sequences with strong metal binding ability, which substantially contributes to the function of the given macromolecule [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Beside the well known human serum albumin (HSA) [1], probably the prion proteins (PrP) [2] are the most studied examples of such sequences.…”

“…Beside the well known human serum albumin (HSA) [1], probably the prion proteins (PrP) [2] are the most studied examples of such sequences. Studies on the metal ion binding of peptides related to the N-terminal of HSA [3][4][5], and those mimicking the octarepeat region of PrP [6][7][8] demonstrated the usefulness of such studies. Besides, several peptides copying the putative metal binding sequences of e.g.…”

Molecular Tailored Histidine‐Based Complexing Surfactants: From Micelles to Hydrogels

“…The pK a values obtained for the terminal amino group were similar to those of similar peptides (Gly-Gly-His, βAla-His) or pseudopeptides (Gly-Gly-Ha, βAla-Ha). In contrast, the pK a of the imidazole ring of the amphiphilic peptides were Gly-Gly-Ha [20] (f).…”