1.
Prediction of the Hydrogen Peroxide-Induced Methionine Oxidation Propensity in Monoclonal Antibodies.
Agrawal, NJ, Dykstra, A, Yang, J, Yue, H, Nguyen, X, Kolvenbach, C, Angell, N
Journal of pharmaceutical sciences. 2018;(5):1282-1289
Abstract
Methionine oxidation in therapeutic antibodies can impact the product's stability, clinical efficacy, and safety and hence it is desirable to address the methionine oxidation liability during antibody discovery and development phase. Although the current experimental approaches can identify the oxidation-labile methionine residues, their application is limited mostly to the development phase. We demonstrate an in silico method that can be used to predict oxidation-labile residues based solely on the antibody sequence and structure information. Since antibody sequence information is available in the discovery phase, the in silico method can be applied very early on to identify the oxidation-labile methionine residues and subsequently address the oxidation liability. We believe that the in silico method for methionine oxidation liability assessment can aid in antibody discovery and development phase to address the liability in a more rational way.
2.
The association between the methionine/valine (M/V) polymorphism (rs1799990) in the PRNP gene and the risk of Alzheimer disease: an update by meta-analysis.
He, J, Li, X, Yang, J, Huang, J, Fu, X, Zhang, Y, Fan, H
Journal of the neurological sciences. 2013;(1-2):89-95
Abstract
BACKGROUND The M/V polymorphism in the PRNP gene has been extensively examined for the association to the risk of Alzheimer disease (AD); however, results from different studies have been inconsistent. The aim of this study is to evaluate the association between the M/V polymorphism in the PRNP gene and the risk of AD. METHODS A meta-analysis was carried out to analyze the association between the M/V polymorphism in the PRNP gene and the risk of AD. RESULTS A total of 4228 cases and 4324 controls in 16 case-control studies were included in the meta-analysis. The results indicated that the variant V allele carriers (VV+MV) had a 13% decreased risk of AD, when compared with the homozygote MM (VV+MV vs. MM: OR=0.87, 95% CI=0.79-0.96, P=0.004). In the subgroup analysis by ethnicity, significant decreased risks of AD were found in the Caucasian V allele carriers (OR=0.85, 95% CI=0.77-0.94, P=0.002), but not in Asian V allele carriers (OR=1.11, 95% CI=0.78-1.57, P=0.57). In the subgroup analysis by age of onset, significant decreased risks of AD were associated with V allele carriers in late-onset Alzheimer disease (OR=0.76, 95% CI=0.62-0.93, P=0.007) but not in early-onset Alzheimer disease (OR=0.86, 95% CI=0.70-1.06, P=0.17). CONCLUSIONS Our results suggest that the M/V polymorphism in the PRNP gene contributes to the susceptibility of Alzheimer disease.