1. Determination of the microscopic and macroscopic acid dissociation constants of glycyl-L-histidyl-L-lysine and related histidine peptides
D L Rabenstein, M S Greenberg, C A Evans Biochemistry. 1977 Mar 8;16(5):977-81. doi: 10.1021/bi00624a026.
Proton magnetic resonance studies of the acid-base chemistry of the glycyl ammonium, histidyl imidazolium, and lysyl ammonium groups of glycyl-L-histidyl-L-lysine and of the glycyl ammonium and histidyl imidazolium groups of glycyl-L-histidine and glycyl-L-histidylglycine are described. Chemical-shift data indicate that, at the molecular level, the glycyl ammonium and the histidyl imidazolium groups are titrated over the same pH range, with the acidity of the imidazolium group some 8 to 10 times that of the glycyl ammonium group, depending on the peptide. The lysyl ammonium group of Gly-His-Lys is much less acidic and is titrated over a higher pH range. Microscopic and macroscopic acid-dissociation constants were determined from chemical-shift data for each of the peptides. It is shown how microscopic formation constants for protonated metal complexes of these ligands, which are being used increasingly as models for the binding of metal ions by proteins, can be calculated from the macroscopic formation constants and the microscopic acid-dissociation constants. The acid-base chemistry of Gly-His-Lys is discussed with respect to its recently discovered biological activity.
2. l-Histidyl-glycyl-glycyl-l-histidine. Amino-acid structuring of the bleomycin-type pentadentate metal-binding environment capable of efficient double-strand cleavage of plasmid DNA
Satomi Ida, Kana Iwamaru, Mikako Fujita, Yoshinari Okamoto, Yuri Kudo, Hiromasa Kurosaki, Masami Otsuka Bioorg Chem. 2015 Oct;62:8-14. doi: 10.1016/j.bioorg.2015.06.007. Epub 2015 Jun 29.
A tetrapeptide, l-histidyl-glycyl-glycyl-l-histidine (HGGH), was synthesized and the pUC19 plasmid DNA cleaving activity by copper(II) complex of HGGH (Cu(II)-HGGH) was investigated. Cu(II)-HGGH showed bleomycin-like DNA cleaving activity and, at 50nM, converted a supercoiled DNA efficiently to a linear DNA in the presence of 500μM H2O2/sodium ascorbate through an oxidative pathway.
3. pH-dependent redox and CO binding properties of chelated protoheme-L-histidine and protoheme-glycyl-L-histidine complexes
Giampiero De Sanctis, et al. J Biol Inorg Chem. 2006 Mar;11(2):153-67. doi: 10.1007/s00775-005-0060-y. Epub 2005 Dec 10.
The pH dependence of redox properties, spectroscopic features and CO binding kinetics for the chelated protohemin-6(7)-L-histidine methyl ester (heme-H) and the chelated protohemin-6(7)-glycyl-L-histidine methyl ester (heme-GH) systems has been investigated between pH 2.0 and 12.0. The two heme systems appear to be modulated by four protonating groups, tentatively identified as coordinated H(2)O, one of heme's propionates, N(epsilon) of the coordinating imidazole, and the carboxylate of the histidine residue upon hydrolysis of the methyl ester group (in acid medium). The pK (a) values are different for the two hemes, thus reflecting structural differences. In particular, the different strain at the Fe-N(epsilon) bond, related to the different length of the coordinating arm, results in a dramatic alteration of the bond strength, which is much smaller in heme-H than in heme-GH. It leads to a variation in the variation of the pKa for the protonation of the N(epsilon) of the axial imidazole as well as in the proton-linked behavior of the other protonating groups, envisaging a cross-talk communication mechanism among different groups of the heme, which can be operative and relevant also in the presence of the protein matrix.
