Mouse anti-Human NCR3 monoclonal antibody, clone z5F7

The action of PdCl2 on phenylhydrazones derived from 2-oxopropionaldehyde, benzoylformaldehyde or butane-2,3-dione led to dinuclear metallacycles 1 [{Pd[2-((NRN)-N-4=(CRCRO)-C-3-O-2)-5-(RC6H3)-C-1]Cl}(2)] (R-1 = H, Pr, NO2 or MeO; R-2 = Me or Ph; R-3, R-4 = H or Me). Compounds 1 reacted with PPh3 to afford [PdCl{kappa C,kappa N-(C-N)} (PPh3)] 2 or [PdCl{kappa C-(C-N)}(PPh3)(2)] 3 (C-N being the metallated hydrazone) which contain one or two phosphine molecules per metal atom respectively, depending on the steric hindrance of the N-donor ligands. The structure of [Pd{2-(NHN=CHCOMe)-5 -O2NC6H3} Cl(PPh3)] has been determined by X-ray diffraction. The bond distances and angles are similar to those reported for related metallacycles. The distance N(1)...O(1) [2.631(4) Angstrom] indicates the presence of a strong intramolecular hydrogen bond between the NH and COMe groups. The C(8)-O(1) [1.222(5) Angstrom], C(8)-C(7)[1.470(5) Angstrom], C(7)-N(2) [1.304(4) Angstrom] and N(1)-N(2) [1.342(4) Angstrom] bond lengths indicate that the complex 3 exists mainly in the keto-hydrazo form. The action of NaOMe on the PPh3 or (PPh3)(2) complexes in MeOH afforded deep violet compounds which do not contain chlorine atoms. The analytical data, IR and NMR spectra showed that deprotonation of the NH group had taken place to give[Pd {2-(N=NCR3=(CRO)-O-2)-5-(RC6H3)-C-1}(PPh3)], by means of an hydrazo-keto azo-enol tautomerization.

Linkage studies have revealed a linkage of mild malaria to chromosome 6p21 that contains the NCR3 gene encoding a natural killer cell receptor, whereas NCR3-412G>C (rs2736191) located in its promoter region was found to be associated with malaria in Burkina Faso. Here we confirmed the association of rs2736191 with mild malaria in a Congolese cohort and investigated its potential cis-regulatory effect. Luciferase assay results indicated that rs2736191-G allele had a significantly increased promoter activity compared to rs2736191-C allele. Furthermore, EMSAs demonstrated an altered binding of two nuclear protein complexes to the rs2736191-C allele in comparison to rs2736191-G allele. Finally, after in silico identification of transcription factor candidates, pull-down western blot experiments confirmed that both STAT4 and RUNX3 bind the region encompassing rs2736191 with a higher affinity for the G allele. To our knowledge, this is the first report that explored the functional role of rs2736191. These results support the hypothesis that genetic variation within natural killer cell receptors alters malaria resistance in humans.