Effect of photo-degradation on the structure, stability, aggregation, and function of an IgG1 monoclonal antibody

Unique Impacts of Methionine Oxidation, Tryptophan Oxidation, and Asparagine Deamidation on Antibody Stability and Aggregation

“…[49][50][51] In the case of photodegraded mAbs, sucrose was also observed to reduce the rate of aggregation, although it had little effect on the rate of Met oxidation. 41 Various observations have been reported for the effects of sucrose on the oxidation of other proteins, including slight protection for interleukin-7 Fc fusion protein 52 and subtilisin, 53 no effect for tumor necrosis factor receptor 1, 54 and slight worsening for granulocyte colony-stimulating factor 55 and recombinant activated factor VII. 51 Moreover, sucrose has been shown to decrease the rate of Asn deamidation (or formation of acidic species) for mAbs 56 and acrylodan-conjugated glucose-binding protein.…”

“…One such mechanism is that these chemical modifications can lead to the formation of covalently cross-linked species between different antibody domains. 20,[39][40][41] Therefore, we used SDS-PAGE to evaluate the formation of reducible and nonreducible cross-linked species of the control, oxidized, and deamidated mAbs (Fig. 5).…”

The Structure of Blood Coagulation Factor XIII Is Adapted to Oxidation

“…In other words, methionine residues embedded in the primary structure of plasma proteins may serve as innate ROS interceptors [ 39 ]. The ability of exposed methionines to scavenge different forms of ROS to protect crucial amino acid residues from being oxidized was previously demonstrated for some plasma proteins [ 40 , 41 , 42 , 43 ]. Hence, that the FXIII-A subunit is exceedingly plentiful in Met residues, many of which are likely to be located on the protein surface and could contribute to primary antioxidant defenses against oxidant-induced injury.…”

Physicochemical Stability of Monoclonal Antibodies: A Review

“…On the other hand, light exposure does not seem to directly alter mAbs secondary and tertiary structures. 107 Liquid forms also seem to be more sensible than lyophilized forms. 108 When exposing high concentration (100 mg/mL) IgG solutions to intense light (30 to 78 h under 8000 lux white fluorescent light, or under International Council for Harmonisation [ICH] Q1B conditions), a yellow coloration appeared, increasing with exposure time, and which was not present when only the formulation buffer was exposed.…”

“…148 Like mannitol, even if used for mechanical properties of the lyophilized formulations, it may also possess stabilization properties toward protein aggregation if remaining in amorphous state, being then more protective. 159 Shah et al 107 showed that methionine may protect mAbs from photodegradation, whereas tryptophan is itself subject to photodegradation, generating reactive oxygen species that may induce photodegradation.…”