Approaches for the detection and analysis of antidrug antibodies to biopharmaceuticals: A review

Antibody-based therapeutic agents and other biopharmaceuticals are now used in the treatment of many diseases. However, when these biopharmaceuticals are administrated to patients, an immune reaction may occur that can reduce the drug's efficacy and lead to adverse side-effects. The immunogenicity of biopharmaceuticals can be evaluated by detecting and measuring antibodies that have been produced against these drugs, or antidrug antibodies. Methods for antidrug antibody detection and analysis can be important during the selection of a therapeutic approach based on such drugs and is crucial when developing and testing new biopharmaceuticals. This review examines approaches that have been used for antidrug antibody detection, measurement, and characterization. Many of these approaches are based on immunoassays and antigen binding tests, including homogeneous mobility shift assays. Other techniques that have been used for the analysis of antidrug antibodies are capillary electrophoresis, reporter gene assays, surface plasmon resonance spectroscopy, and liquid chromatography-mass spectrometry. The general principles of each approach will be discussed, along with their recent applications with regards to antidrug antibody analysis.     

Polymerization of 2,4-hexadiyn-1,6-diol by chemical vapor deposition

2,4-Hexadiyn-1,6-diol (HDO) was polymerized on glass and silicon plates by chemical vapor deposition without transition metal catalysis to form homogeneous thin films. Structural properties of the films were investigated by FT-IR, UV-visible, Raman, x-ray diffraction, and XPS spectroscopic analyses. The structure of CVD-polymerized HDO (CVD-PHDO) films was different from that of metathesis polymerized HDO (metathesis-PHDO), showing a polyacene-based structure but no polyene structure with acetylenic side groups. © 1996 John Wiley & Sons, Inc.     

Redox equilibria of iron oxides in aqueous-based magnetite dispersions: effect of pH and redox potential

The effect of pH and redox potential on the redox equilibria of iron oxides in aqueous-based magnetite dispersions was investigated. The ionic activities of each dissolved iron species in equilibrium with magnetite nanoparticles were determined and contoured within the Eh-pH framework of a composite stability diagram. Both standard redox potentials and equilibrium constants for all major iron oxide redox equilibria in magnetite dispersions were found to differ from values reported for noncolloidal systems. The "triple point" position of redox equilibrium among Fe(II) ions, magnetite, and hematite shifted to a higher standard redox potential and an equilibrium constant which was several orders of magnitude higher. The predominant area of magnetite stability was enlarged to cover a wider range of both pH and redox potentials as compared to that of a noncolloidal magnetite system.     

稳态荧光探针法测定临界胶束聚集数

以芘为荧光探针、二苯甲酮为猝灭剂,用稳态荧光探针法测定了SDS和AS的胶束聚集数(Nm).以芘的饱和水溶液为溶剂配制表面活性剂溶液,二苯甲酮的适宜浓度取小于1.00 mmol•L－1时,可以获得满意的实验结果.当表面活性剂溶液浓度为5～9倍cmc时,Nm随表面活性剂浓度增大而线性增大,而随温度的变化略有波动.cSAA=cmc时,Nm值为一本征值,定义为临界胶束聚集数[Nm].[Nm]值可从Nm－cSAA实验曲线外延得到.25℃时SDS的临界胶束聚集数[Nm]为57;40℃时SDS的[Nm]为49,AS的[Nm]为55.     

Surface-enhanced Raman scattering of nucleic acid components in silver sol: Uracil and its derivatives

The surface-enhanced Raman scattering (SERS) of uracil, uridine, 2′-deoxyuridine and 5′-rUMP adsorbed on aqueous silver sol was investigated. Uracil was found to adsorb as the N-3 deprotonated form, which underwent a reorientation from the situation where the base was perpendicular to the surface to the situation where the base lay flat on the surface as the surface charge was made more negative. The N-3 deprotonated molecules of uridine, 2′-deoxyuridine and 5′-rUMP were found to lie flat on the silver surface regardless of the bulk concentration and the silver surface charge.     

Multiple intramolecular hydrogen bonds in 2,4‐di‐tert‐butyl‐6‐[N‐(2,6‐diisopropylphenyl)‐P,P‐diphenylphosphorimidoyl]phenol

The title compound, C₃₈H₄₈NOP, isolated from the reaction of (2‐diphenylphosphanyl‐4,6‐di‐tert‐butyl)phenol with 2,6‐diisopropylphenyl azide at 273 K, can act as an N,O‐bidentate ligand. Crystal structure analysis shows a deviation from ideal tetrahedral symmetry around the P atom. The molecule exists as a monomer in the solid state, whose conformation is stabilized via multiple intramolecular hydrogen bonds. Geometric parameters from both experimental and theoretical calculations are compared.     

Environments of ethidium binding to allosteric Dna: II. Accessibility, mobility and mode of binding

DNA binding compounds were previously shown to bind to the right-handed DNA forms and hybrid B-Z forms in a highly cooperative manner and indicate that structural specificity plays a key role in a ligand binding to DNA. In this study, the modes of binding and structural specificity of agents to unusual DNA are examined by a variety of fluorescence techniques (intensity, polarization and quenching, etc.) to explore a reliable method to detect the association environment of ligands to deoxyoligonucleotides initially containing a B-Z junction between the left-handed Z-DNA and right-handed B-DNA. The results of fluorescence energy transfer measurement demonstrated that the ligand molecules bind to the allosterically converted DNA structures by intercalation. In the absence of high-resolution structural data, this fluorescence energy transfer measurement allowed reliable measures and infer the binding environment of ligands to the allosteric DNA structures.