Comprehensive characterization of higher order structure changes in methionine oxidized monoclonal antibodies via NMR chemometric analysis and biophysical approaches.

The higher order structure (HOS) of monoclonal antibodies (mAbs) is an important quality attribute with strong contribution to clinically relevant biological functions and drug safety. Due to the multi-faceted nature of HOS, the synergy of multiple complementary analytical approaches can substantially improve the understanding, accuracy, and resolution of HOS characterization. In this study, we applied one- and two-dimensional (1D and 2D) nuclear magnetic resonance (NMR) spectroscopy coupled with chemometric analysis, as well as circular dichroism (CD), differential scanning calorimetry (DSC), and fluorescence spectroscopy as orthogonal methods, to characterize the impact of methionine (Met) oxidation on the HOS of an IgG1 mAb.

Biopharmaceutical Industry Practices for Sequence Variant Analyses of Recombinant Protein Therapeutics.

The application of advanced methodologies such as next-generation sequencing (NGS) and mass spectrometry (MS) to the characterization of cell lines and recombinant proteins has enabled the highly sensitive detection of sequence variants (SVs). However, although these approaches can be leveraged to provide deep insight into product microheterogeneity caused by SVs, they are not used in a standardized manner across the industry. Currently, there is little clarity and consensus on the utilization, timing, and significance of SV findings.

-Tc/Re-tricarbonyl complexes with tridentate aminocarboxyphosphonate ligands: suitability of the phosphonate group in chelate ligand design of new imaging agents.

Ligands that coordinate via dianionic phosphonate groups have not been widely utilized in radiopharmaceuticals. -(phosphonomethyl)iminodiacetic acid (, PMIDA) and (phosphonomethyl)glycine (, PMG) were investigated as new chelators for the Tc/Re-tricarbonyl "core" (-M(CO), M = Tc, Re) present in a major class of radiopharmaceuticals. fac-M(CO)(PMIDA) and fac-M(CO)(PMG) complexes were studied by HPLC and H/C/P NMR methods for M = Re ( and ) and by HPLC for M = Tc ( and ).

Linear Bidentate Ligands (L) with Two Terminal Pyridyl N-Donor Groups Forming Pt(II)LCl Complexes with Rare Eight-Membered Chelate Rings.

NMR and X-ray diffraction studies were conducted on Pt(II)LCl complexes prepared with the new N-donor ligands N(SOR)Me dpa (R = Me, Tol; n = 2, 4). These ligands differ from N(H)dpa (di-2-picolylamine) in having the central N within a tertiary sulfonamide group instead of a secondary amine group and having Me groups at the 6,6'-positions ( n = 2) or 3,3',5,5'-positions ( n = 4) of the pyridyl rings. The N(SOR)3,3',5,5'-Medpa ligands are coordinated in a bidentate fashion in Pt( N(SOR)3,3',5,5'-Medpa)Cl complexes, forming a rare eight-membered chelate ring.