Glycylglycyl-L-histidine

Note. Abbreviations used imH, imidazole imFL, neutral imidazolium ylide (deprotonated at C-2) glyglyhis, glycylglycyl-L-histidine bzimH, benzimidazole biimH2, 2,2 -biimidazole pyzH, pyrazole pz, pyrazine pzH, pyrazinium monocation 4-pic, 4-picoline isn, isonicotinamide py, pyridine 4-acpy, 4-acetylpyridine dmpzH. 2,6-dimethylpyrazinium monocation 4,4 -bpyH, 4,4 -bipyridinium monocation. T = 25°C unless otherwise stated. 

Tetra-p-methoxyphenylporphyrin Tetra-p-sulfophenylporphyrin Glycylglycyl-l-histidine-N-methylamide jV,A"-Ethylenebis(2-hydroxypropiophenoneimine) Hexafluoroacetylacetone The tripeptide of a-aminoisobutyric acid cis-1,2-Dicy anoethylene-1,2-dithiolato Al-(4-Imidazolylmethylidyneimine)-N -(2-hydroxy-5-chlorobenzyliphenoneiminelphenylene Tetra-n-butylammonium 5,10,15,20-Tetra-p-chlorophenylporphyrin 1,4-Bis( 1 -oxa-4,10-dithia-7-azacyclododecan-7 -y lmethyl Ibenzene Bis[AlA/ -bis(2-... 

The presence of L-histidine as the third amino acid residue in tripeptide complexes of Cu(II) drastically decreases their susceptibility to both nucleophilic attack and acid attack (11, 12). Thus, the doubly deprotonated complex of glycylglycyl-L-histidine (Cu(H 2gly-gly-his) shown in Structure I is relatively slow to react with the nucleophilic tri-ethylenetetramine (trien) since this reaction is seven orders of magnitude slower than the corresponding reaction with Cu(H 2gly-gly-gly). The... 

Fig. 18. Structure of the copper-binding peptide, glycylglycyl-L-histidine-A -methylamide illustrating the coordination state and peptide conformation. Figure modified from Camerman etal. (1976).

MOLECULAR DESIGN THEORETICAL AND SOLUTION STUDIES ON COPPER(II) COMPLEX OF GLYCYLGLYCYL-L-HISTIDINE-N-METHYL AMIDE,... 

Considering these features, as well as the geometry of the ligand array in the native protein and the nature of the donor groups, a simple peptide molecule glycylglycyl-L-histidine was designed to mimic the copper transport site. A detailed study of Cu(II) binding to this peptide has been reported [4]. However, this peptide lacked... 

Conformation of glycylglycyl-L-histidine-N-methyl amide may be represented by a set of torsional angles, < i, ( 2 2 J d described about the... 

Fig. 5. Conformational energy surface of glycylglycyl-L-histidine-N-methyl amide-Cu(II) complex as a function of torsional angles and x ( i=—80°, y/%=—2(f, < 2 = — 180°, v 3=—20°) in kcal mole relative to the global minimum marked x. A, B, C and D are the conformations satisfying the constraint, viz. inter-nitrogen distances suitable for forming a square planar complex.

Fig. 6. A perspective of the predicted stable conformation of Copper (II)-glycylglycyl-L-histidine-...

A perspective of the minimum energy conformation of the complex is shown in Figure 6. We observe from theoretical studies that the Cu(II) atom prefers a square planar environment. Detailed account of our study and a comparison of conformations of the synthetic molecule glycylglycyl-L-histidine-N-methyl amide with the natural analogue L-aspartyl-L-alanly-L-histidyl-N-methyl amide will be presented elsewhere. 

The complexation reactions occurring between C moles of Cu(II) ion M, Ch moles of hydrogen ion H, C moles of ligand anion glycylglycyl-L-histidine-N-methyl amide A, can be represented by the following general equilibrium reaction ... 

The stability constants and the pK values are listed in Table I. For the purpose of comparison, the values for glycylglycyl-L-histidine-Cu(II) system worked out earlier [4], are included. It can be seen that the methyl amide form of the peptide bound Cu(II) more strongly than did the carboxyl free peptide. 

Comparison of log stability constants (logfipgr) of complex species MpHffAr and M HgAV (M=Cu(II), A=glycylglycyl-L-histidine and A =glycylglycyl-L-histidine-N-methyl amide) in O.lSMNaCl at 25°C... 

Fig. 9. Visible spectra of 1 1 Cu(II)-ligand complexes. A, Cu(II)-human albumin B, Cu(II)-glycylglycyl-L-histidine C, Cu(II)-glycylglycyl-L-histidine-N-methyl amide.

Fig. 10. Structure of Cu(II)-glycylglycyl-L-histidine-N-methyl amide complex species (MH 2A).

Inoue S, Kawanishi S (1989) ESR evidence for superoxide, hydroxyl radicals and singlet oxygen produced from hydrogen peroxide and nickel(II) complex of glycylglycyl-L-histidine. Biochem Biophys Res Commum 159 445-451 Inoue S, Yamamoto K, Kawanishi S (1990) DNA damage induced by metabolites of o-phenylphenol in the presence of copper(II) ion. Chem Res Toxicol 3 144-149... 

CliHigCuNsOu, Glycylglycyl-L-histidine-N-methylamide-copper(II) monohydrate, 42B, 802... 

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