A study of the comparative donor properties to Cu II of the terminal amino and imidazole nitrogens in peptides

Abstract

The synthesis of the tetrapeptides Ala-Gly-Gly-His, Boc-Ala-Gly-Gly-His (Boc = t-butoxycarbonyl), Ala-G ly-G ly-H is(n-bom) (x-bom = N"benzoxymethyl), Ala-Gly-G ly-H is-OMe, and Ala-Gly-Pro-H is is reported, together with the results of a pH-metric and spectroscopic (absorption, c.d., and e.s.r.) study of their complexes with H + and Cu". The work was designed to study the initial site of binding to Cu" in peptides containing both a terminal amino nitrogen and a histidyl residue. Results show that the n-N of the imidazole ring of the histidyl residue is the primary anchoring site for copper(it) co-ordination, and that the next nitrogen to bond can be the terminal amino N, forming a macrocyclic chelate ring.

The role of terminal amino group and histidine at the fourth position in the metal ion binding of oligopeptides revisited: Copper(II) and nickel(II) complexes of glycyl-glycyl-glycyl-histamine and its N-Boc protected derivative

“…The determined spectroscopic parameters of Cu(BGGGHa) ( Table 2), represent a stronger ligand field around copper(II). In line with previous findings, a macrochelate formation with participation of the N-terminal amino group and the imidazole moiety can be suggested [1,9,13,16,18].…”

“…carnosine (β-alanylhistidine) [34,35], His-Gly [34] His-His [36] or His-His-Gly-Gly [37]. The possibility of dimer formation was also mentioned in the case of Ala-Gly-Gly-His [13], however, no spectroscopic evidence was found. The proton release of the CuL complex of GGGHa results in remarkable changes on the Vis and EPR spectra (Figs.…”

“…The metal binding features of oligopeptides, including the effect of the number and position of histidine residues within the peptide chain have been summarized in a couple of reviews within the last decade [1,9,10]. There have been a number of systematic studies attempting to explore the role of the terminal amino group and a histidine at the fourth or higher position in the peptide sequence, as primary coordination sites for copper(II) and nickel(II) [11][12][13][14][15][16]. However, the obtained results were sometimes contradictory and generated some debates.…”

Copper effective binding with 32–62 and 94–125 peptide fragments of histone H2B

“…This is the main species formed at physiological pH. The value log K*= −15.78 is similar to the values found in the literature for the 3N species of analogous copper-peptide complexes [46], as well as with the tetrapeptide, Boc-AGGH (log K* = −15,68) [50]. The amide nitrogen coordination is further sustained by the presence of the characteristic Ν amide → Cu(II) CT band at 309 nm in the CD spectrum recorded at pH 7.5 (Table 3, Fig.…”

Molecular mechanisms in nickel carcinogenesis: modeling Ni(II) binding site in histone H4.

“…They are more acidic than other simple peptides, about one order of magnitude more acidic than histidine in Boc-AGGH, Ac-GGGH, and Ac-GGH (7.19, 7.21, and 7.18, respectively), where glycine instead of arginine or lysine residues are close to the anchoring site for metal ions. It is interesting to note that the pK a (NH im + ) values for our motifs are of the same order of magnitude as that of N-terminal free peptides and where electronwithdrawing groups substitute a hydrogen at the pyrrolic nitrogen (35). In this case the less basicity is due both to the electrostatic effect of the positive charge from NH 3 + terminus and to the inductive effect of the substituting group.…”