Flaviviruses are a group of human pathogenic, enveloped RNA viruses that includes dengue (DENV), yellow fever (YFV), West Nile (WNV), and Japanese encephalitis (JEV) viruses. Cross-reactive antibodies against Flavivirus have been described, but most of them are generally weakly neutralizing. In this study, a novel monoclonal antibody, designated mAb 2A10G6, was determined to have broad cross-reactivity with DENV 1–4, YFV, WNV, JEV, and TBEV. Phage-display biopanning and structure modeling mapped 2A10G6 to a new epitope within the highly conserved flavivirus fusion loop peptide, the 98DRXW101 motif. Moreover, in vitro and in vivo experiments demonstrated that 2A10G6 potently neutralizes DENV 1–4, YFV, and WNV and confers protection from lethal challenge with DENV 1–4 and WNV in murine model. Furthermore, functional studies revealed that 2A10G6 blocks infection at a step after viral attachment. These results define a novel broadly flavivirus cross-reactive mAb with highly neutralizing activity that can be further developed as a therapeutic agent against severe flavivirus infections in humans.
A family of linear hexapeptides composed of histidine on the N‐terminus followed by aromatic amino acid(s) and positively charged amino acid(s) has been identified through a three‐step screening of a synthetic solid phase library. These peptides were able to recognize human immunoglobulin G (HIgG) through its Fc region, and their selectivity to Fc is comparable to Protein A. This is the first known report of short peptides that are able to bind HIgG by recognizing its Fc portion. One of the ligands from the identified family, HWRGWV, was examined for its ability to isolate HIgG from complex mixtures. It was found that HWRGWV possessed the potential to purify HIgG from complete mammalian cell culture medium containing 10% fetal calf serum with purity comparable to commercially available resins, but using milder elution conditions. HWRGWV bound all HIgG subclasses and IgGs from bovine, mouse, goat, and rabbit. The broad affinity spectrum as well as its Fc recognition ability may be useful in capturing and detecting both polyclonal and monoclonal antibodies.
Articles you may be interested inThe dissociative chemisorption of methane on Ni (111): The effects of molecular vibration and lattice motion Summary Abstract: Collision induced dissociation and desorption: CH4 and CO on Ni (111) J. Vac. Sci. Technol. A 6, 903 (1988); 10.1116/1.575027 Lack of translational energy activation of the dissociative chemisorption of CO on Ni(111) J. Chem. Phys. 87, 723 (1987); 10.1063/1.453569 Activated dissociative chemisorption of CH4 on Ni(111): Observation of a methyl radical and implication for the pressure gap in catalysisThe dissociative chemisorption of methane at an atop-atom site on a (111) surface of nickel is treated using a many-electron embedding theory to describe bonding, modeling the lattice as a 4I-atom, three layer cluster. Ab initio valence orbital configuration interaction (multiple parent) calculations carried out on a local surface region permit an accurate description of bonding at the surface. Ni 3d orbitals are explicitly included on seven nickel atoms on the surface. The calculated activation energy of CH 4 adsorbed at an atop Ni site to produce CH 3 and H coadsorbed at separated threefold sites is 17 kcallmol. The dissociation of CH 4 to CH 3 (ads) + H (ads) is predicted to be 2.8 kcallmol exothermic. The Ni 3d orbitals contribute to the bonding by directly mixing with methane C-H orbitals during the dissociation process and through a direct interaction of 3d 9 and 3d 10 configurations at the transition state. The dissociation pathway and the bonding properties of adsorbed CH 4 and coadsorbed CH 3 and H are discussed.
The adsorption of methyl on the (1 11) surface of nickel is treated by using a many-electron embedding theory to describe bonding, modeling the lattice as a 28-atom, three-layer cluster. Ab initio valence orbital configuration interaction (multiple parent) calculations carried out on a local surface region permit an accurate description of bonding at the surface. Calculated adsorption energies for CH3 on the Ni( 11 1) surface are 39 kcal/mol at the 3-fold sites and 36 and 34 kcal/mol at the bridge and the atop atom sites with the equilibrium Ni-C distances of 2.35, 2.34, and 2.03 A, respectively. Calculated CH3-(Ni surface) perpendicular stretching frequencies are 369, 296, and 416 cm-l for the 3-fold, bridge, and atop sites. In the equilibrium geometry methyl hydrogens are in a plane parallel to the surface with a nearly tetrahedral structure. A low C-H vibrational frequency is calculated at 2627 cm-' if one of the hydrogens is tilted to give a C-H bond parallel to the surface, and CHI is shifted away from the 3-fold center by 0.67 au, which puts one of the hydrogens directly above a Ni atom. This geometry is only I .6 kcal/mol higher in energy than the calculated equilibrium geometry for which normal C-H vibrational frequencies of around 3000 cm-' are calculated. The reaction of chemisorbed CH2(ads) + H(ads) = CH,(ads) on the surface is 13 kcal/mol exothermic. An energy barrier occurs when CHI and H are moved from infinite separation to form CH3. A combination of covalent s and d bonding characterizes the bonding of CH3 to the nickel surface.
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