Anti-Sheep CD1 monoclonal antibody

CD1 molecules present lipid antigens to T-cells in early stages of immune responses. Whereas CD1-lipid-T-cell receptors interactions are reasonably understood, molecular details on initial trafficking and loading of lipids onto CD1 proteins are less complete. We present a molecular dynamics (MD) study of human CD1d, the isotype that activates iNKT cells. MD simulations and calculations of properties and Poisson-Boltzmann electrostatic potentials were used to explore the dynamics of the antigen-binding domain of the apo-form, CD1d complexes with three lipid-antigens that activate iNKT cells and CD1d complex with GM2AP, a protein that assists lipid loading onto CD1 molecules in endosomes/lysosomes. The study was done at pH 7 and 4.5, values representative of strongly acidic environments in endosomal compartments. Our findings revealed dynamic features of the entrance to the hydrophobic channels of CD1d modulated by two alpha helices with sensitivity to the type of lipid. We also found lipid- and pH-dependent dynamic changes in three exposed tryptophans unique to CD1d among the five human CD1 isotypes. On the basis of modelled structures, our data also revealed external effects produced by the helper protein GM2AP only when it interacts in its open form, thus suggesting that the own assistant protein also adapts conformation to association with CD1d.

A di-nuclear azido-bridged Cd(II) 1-D coordination polymer [Cd-2(H2LpentOMe)(mu(1,1)-N-3)(2)](n) (1) has been successfully synthesized using less explored bi-compartmental Schiff base ligand (H2LpentOMe) and characterized by elemental analysis, FT-IR, FT-Raman, UV-Visible, SEM-EDAX, powder X-ray diffraction and fluorescence spectroscopy. Solid-state X-ray single crystal study revealed two different geometrical environment of Cd metal centres with distorted square pyramidal (Cd1) and distorted pentagonal bipyramid (Cd2). Overall, small-sized azide ions in asymmetric unit act as mu(1,1) bridging mode. Geometry is optimized in gas phase using ORCA 3.0.3 and B3LYP level TZVP basis set to explain frontier molecular orbitals (FMO), molecular electrostatic potential (MEP) and global reactivity. The HOMO-LUMO energy gap (3.434 Ev) suggests that chemical reactivity of complex 1 is low but fairly stable. Moreover, molecular electrostatic potential map was drawn to identify reactive regions in terms of electrophilic and nucleophilic. The steady state and time-resolved fluorescence properties have been explored in DCM and solid-state condition at room temperature. Complex 1 exhibit bi and tri-exponential decay in DCM as well as solid-state. The fluorescence behaviours are predominantly intra-ligand in nature (pi -> pi*) with lifetimes in the range (1.16-1.11 ns). Solvatochromism has been reported to show solvent dependent absorption and fluorescence spectral changes. Fascinatingly, red shifted solvatochromism was observed upon increasing solvent polarity. Finally, concentration dependent antimicrobial activity was investigated against two standard bacterial strains (Staphylococcus aureus (ATCC 25923) and Methicillin-resistant Staphylococcus aureus (MRSA) where 250 mu g/ml concentration of complex 1 is sufficient to show the anti-microbial effect.