D-Histidine

Stereoselective amino acid analysis has increasingly moved into the scope of interest of the scientific community. In this work, we report a study on the chiral separation of underivatized D,L-His by ligand exchange capillary electrophoresis (LECE), utilizing accurate ex ante calculations. This has been obtained by the addition to the background electrolytes (BGE) of NaClO(4) which renders the separations "all in solution processes", allowing to accurately calculate in advance the concentrations of the species present in solution and to optimize the system performances. To this aim, the formation of ternary complexes of Cu(2+) ion and L-lysine (L-Lys) or L-ornithine (L-Orn) with L- and D-histidine (His), and histamine (Hm) have been studied by potentiometry and calorimetry at 25 °C and with 0.1 mol dm(-3) (KNO(3)) in aqueous solution. The ternary species [Cu(L)(L-His)H](+) and [Cu(L)(D-His)H](+) (where L = L-Lys or L-Orn) show a slight but still detectable stereoselectivity, and the determination of ΔH° and ΔS° values allowed the understanding of the factors which determine this phenomenon.

Nickel is an important cofactor for several microbial enzymes. The ATP-dependent NikABCDE transporter is one of several types of uptake pathways known to be important for nickel acquisition in microbes. The Escherichia coli NikA periplasmic binding protein is structurally homologous to the di- and oligopeptide binding proteins, DppA and OppA. This structural similarity raises interesting questions regarding the evolutionary relationships between the recognition of nickel ions and short peptides. We find that in defined minimal growth medium NikABCDE transports nickel ions in the presence of exogenously added L-histidine (L-His), but not D-histidine. Both nickel uptake in cells and nickel binding to purified NikA showed an L-His concentration dependence consistent with recognition of a Ni-(L-His)₂ complex. This discovery reveals parallels to the transport of other metal complexes, notably iron, and suggests the structural diversity of nickel transporters may arise from the need to recognize extracellular nickel complexed with different organic ligands, whether they be exogenously or endogenously produced.

We have prepared L- and D-deoxypolypeptides (DOPPs) by selective reduction of appropriately protected polyhistidines with borane, reducing the carbonyl groups to methylenes. The result is a chiral polyamine, not amide, with a mainly protonated backbone and chirally mounted imidazolylmethylene side chains that are mostly unprotonated at neutrality because of the nearby polycationic backbone. We found that, in contrast with the D-octahistidine DOPP, the L-octahistidine DOPP is able to cooperatively bind to a D-polyuridylic acid RNA; this is consistent with results of previous studies showing that, relative to D-histidine, L-histidine is able to more strongly bind to RNA. The L-DOPP was also a better catalyst for cleaving the RNA than the D-DOPP, consistent with evidence that the L-DOPP uses its imidazole groups for catalysis, in addition to the backbone cations, but the D-DOPP does not use the imidazoles. The L-DOPP bifunctional process probably forms a phosphorane intermediate.

Although zinc (Zn) is an essential trace element, excess Zn causes neuronal death following transient global ischemia and plays a central role in the pathogenesis of vascular-type dementia. In this study, we developed a rapid and convenient screening system for substances that prevent Zn-induced neurotoxicity by using GT1-7 cells (immortalized hypothalamic neurons), with the aim of identifying a treatment for vascular-type dementia. Among tested, we found a protective substance in the extract of round herring (Etrumeus teres), and determined its structure as l-histidine. Analysis of the structure-activity relationship by using histidine analogues revealed that both l-histidine and d-histidine exhibit the same neuroprotective activity. Furthermore, we investigated the molecular mechanisms underlying the protective effect of histidine on Zn-induced neurotoxicity using Zn imaging and gene expression analysis, and found that histidine protects against Zn-induced neurotoxicity not by inhibiting Zn chelation, thereby preventing increases in intracellular Zn(2+).