Reaction Mechanisms of Histidine and Carnosine with Hypochlorous Acid Along with Chlorination Reactivity of N-Chlorinated Intermediates: A Computational Study.

Hypochlorous acid (HOCl) released from activated leukocytes not only plays a significant role in the human immune system but is also implicated in numerous diseases including atherosclerosis and some cancers due to its inappropriate production. Histidine (His) and carnosine (Car), as a respective mediator and protective agent of HOCl damage, have attracted considerable attention; however, their detailed reaction mechanisms are still unclear. In this study, using a His residue with two peptide bond groups (HisRes) as a model, the reaction mechanisms of HisRes and Car including NεH and NδH tautomers with HOCl along with the chlorination reactivity of N-chlorinated intermediates were investigated by quantum chemical methods. The obtained results indicate that in the imidazole side chain, the pyridine-like N is the most reactive site rather than the pyrrole-like N, and the kinetic order of all of the possible reaction sites in HisRes follows pyridine-like N > imidazole Cδ ≫ imidazole Cε > pyrrole-like N, while that in Car is pyridine-like N ≫ imidazole Cδ ≫ amide N. As for N-chlorinated intermediates at imidazole, although the unprotonated form has a low chlorination reactivity as expected, it can still chlorinate tyrosine. Especially, the protonated form exhibits similar ability to HOCl, causing secondary damage in vivo. N-Chlorinated Car features higher internal chlorine migration ability than its intermolecular transchlorination, preventing further HOCl-induced damage. Additionally, a generally overlooked nucleophilic Cl- shift is also found in N-chlorinated Car/HisRes, indicating that nucleophilic sites in biomolecules also need to be considered. The outcomes of this study are expected to expand our understanding of secondary damage and protective mechanisms involved in HOCl in humans.

HL2 on chromosome 7D of wheat (Triticum aestivum L.) regulates both head length and spikelet number.

KEY MESSAGE: A major QTL QSpl.nau-7D, named HL2, was validated for its effects on head length and kernel number per spike using NIL, and mapped to a 0.2 cM interval using recombinants. Improvement in wheat inflorescence traits such as spike or head length and spikelet number provides an important avenue to increase grain yield potential. In a previous study, QSpl.nau-7D, the major QTL for head length on chromosome 7D, was identified in the recombinant inbred lines derived from Nanda2419 and Wangshuibai. To validate and precisely map this QTL, the Wangshuibai allele was transferred to elite cultivar Yangmai15 through marker-assisted selection. Compared with the recurrent parent, the resultant near-isogenic line (NIL) yielded not only 28% longer spikes on the average but also more spikelets and kernels per spike. Moreover, the NIL had a lower spikelet density and did not show significant kernel weight change. In the F2 population derived from the NIL, QSpl.nau-7D acted like a single semi-dominant gene controlling head length and was therefore designated as Head Length 2 (HL2). With this population, a high-density genetic map was constructed mainly using newly developed markers, and 100 homozygous recombinants including 17 genotypes were obtained. Field experiments showed that the recombinants carrying the 0.2-cM interval flanked by Xwgrb1588 and Xwgrb1902 from Wangshuibai produced longer spikes than those without this Wangshuibai allele. Comparative mapping of this interval revealed a conserved synteny among cereal grasses. HL2 is beneficial to wheat breeding for more kernels per spike at a lower spikelet density, which is a favored morphological trait for Fusarium head blight resistance.