Abstract:
:Non-enzymatic glycation is a challenging post-translational modification to characterize due to the structural heterogeneity it generates in proteins. Glycation has become increasingly recognized as an important product quality attribute to monitor, particularly for the biotechnology sector, which produces recombinant proteins under conditions that are amenable to protein glycation. The elucidation of sites of glycation can be problematic using conventional collision-induced dissociation (CID)-based mass spectrometry because of the predominance of neutral loss ions. A method to characterize glycation using an IgG1 monoclonal antibody (mAb) as a model is reported here. The sugars present on this mAb were derivatized using sodium borohydride chemistry to stabilize the linkage and identified using CID-based MS(2) mass spectrometry and spectral search engines. Quantification of specific glycation sites was then done using a targeted MS(1) based approach, which allowed the identification of a glycation hot spot in the heavy chain complementarity-determining region 3 of the mAb. This targeted approach provided a path forward to developing a structural understanding of the propensity of sites to become glycated on mAbs. Through structural analysis we propose a model in which the number and 3-dimensional distances of carboxylic acid amino acyl residues create a favorable environment for glycation to occur.
journal_name
MAbsjournal_title
mAbsauthors
Saleem RA,Affholter BR,Deng S,Campbell PC,Matthies K,Eakin CM,Wallace Adoi
10.1080/19420862.2015.1046663subject
Has Abstractpub_date
2015-01-01 00:00:00pages
719-31issue
4eissn
1942-0862issn
1942-0870journal_volume
7pub_type
杂志文章相关文献
mAbs文献大全abstract::Plasmacytoid dendritic cells (pDCs) play a central role for both innate and adaptive antiviral responses, as they direct immune responses through their unique ability to produce substantial concentrations of type I interferon (IFNs) upon viral encounter while also activating multiple immune cells, including macrophage...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2018.1451283
更新日期:2018-05-01 00:00:00
abstract::Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched ...
journal_title:mAbs
pub_type: 杂志文章,评审
doi:10.4161/mabs.3.5.16968
更新日期:2011-09-01 00:00:00
abstract::Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory disease in infants and young children worldwide. Currently, treatment is supportive and no vaccines are available. The use of newborn lambs to model hRSV infection in human infants may provide a valuable tool to assess safety and efficacy o...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2018.1470727
更新日期:2018-07-01 00:00:00
abstract::In recent years, capillary electrophoresis-sodium dodecyl sulfate (cSDS) has been widely used for high resolution separation and quantification of the fragments and aggregates of monoclonal antibodies (mAbs) to ensure the quality of mAb therapeutics. However, identification of the low-molecular-weight (LMW) and high-m...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2019.1646554
更新日期:2019-10-01 00:00:00
abstract::There are currently ~25 recombinant full-length IgGs (rIgGs) in the market that have been approved by regulatory agencies as biotherapeutics to treat various human diseases. Most of these are based on IgG1k framework and are either chimeric, humanized or human antibodies manufactured using either Chinese hamster ovary...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.19868
更新日期:2012-05-01 00:00:00
abstract::Hepatitis B virus (HBV) produces large (L), middle (M), and small (S) envelope proteins, alternatively referred to as hepatitis B surface antigen (HBsAg). Currently, yeast-derived S protein serves as the preventive vaccine, while hepatitis B immune globulin (HBIG) concentrated from pooled plasma of vaccine recipients ...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2015.1134409
更新日期:2016-01-01 00:00:00
abstract::The linear pharmacokinetics (PK) of therapeutic monoclonal antibodies (mAbs) can be considered a class property with values that are similar to endogenous IgG. Knowledge of these parameters across species could be used to avoid unnecessary in vivo PK studies and to enable early PK predictions and pharmacokinetic/pharm...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2018.1462429
更新日期:2018-07-01 00:00:00
abstract::Site-specific antibody-drug conjugates (ADCs) are designed to overcome the heterogeneity observed with first-generation ADCs that use random conjugation to surface-exposed lysine residues or conjugation to interchain disulfide bonds. Despite significantly enhanced homogeneity, however, the production of site-specific ...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2019.1624127
更新日期:2019-08-01 00:00:00
abstract::Recombinant antibody single-chain variable fragments (scFv) are difficult to purify homogeneously from a protein complex mixture. The most effective, specific and fastest method of purification is an affinity chromatography on Protein L (PpL) matrix. This protein is a multi-domain bacterial surface protein that is abl...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2015.1116657
更新日期:2016-01-01 00:00:00
abstract::Bispecific antibodies can uniquely influence cellular responses, but selecting target combinations for optimal functional activity remains challenging. Here we describe a high-throughput, combinatorial, phenotypic screening approach using a new bispecific antibody target discovery format, allowing screening of hundred...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2020.1859049
更新日期:2021-01-01 00:00:00
abstract::Currently, almost all FDA approved therapeutic antibodies (except ReoPro, Lucentis and Cimzia which are Fabs), and the vast majority of those in clinical trials are full-size antibodies mostly in IgG1 format of about 150 kDa size. A fundamental problem for such large molecules is their poor penetration into tissues (e...
journal_title:mAbs
pub_type: 杂志文章,评审
doi:10.4161/mabs.1.1.7480
更新日期:2009-01-01 00:00:00
abstract::MPDL3280A is a human monoclonal antibody that targets programmed cell death-1 ligand 1 (PD-L1), and exerts anti-tumor activity mainly by blocking PD-L1 interaction with programmed cell death-1 (PD-1) and B7.1. It is being investigated as a potential therapy for locally advanced or metastatic malignancies. The purpose ...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2015.1136043
更新日期:2016-01-01 00:00:00
abstract::Fragmentation in the hinge region of an IgG1 monoclonal antibody (mAb) can affect product stability, potentially causing changes in potency and efficacy. Metals ions, such as Cu(2+), can bind to the mAb and undergo hydrolysis or oxidation, which can lead to cleavage of the molecule. To better understand the mechanism ...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2015.1062193
更新日期:2015-01-01 00:00:00
abstract::Biological therapies have revolutionized the treatment of several cancers and systemic immune-mediated inflammatory conditions. Expiry of patents protecting a number of biologics has provided the opportunity to commercialize highly similar versions, known as biosimilars. Biosimilars are approved by regulatory agencies...
journal_title:mAbs
pub_type: 杂志文章,评审
doi:10.1080/19420862.2018.1484977
更新日期:2018-08-01 00:00:00
abstract::Monoclonal antibody (mAb) therapeutics have tremendous potential to benefit patients with lung diseases, for which there remains substantial unmet medical need. To capture the current state of mAb research and development in the area of respiratory diseases, the Research Center of Respiratory Diseases (CEPR-INSERM U11...
journal_title:mAbs
pub_type:
doi:10.1080/19420862.2016.1196521
更新日期:2016-08-01 00:00:00
abstract::The plasticity of natural immunoglobulin repertoires can be exploited for the generation of phage display libraries. Secondary lymphoid organs, such as the spleen and the lymph nodes, constitute interesting sources of diversity because they are rich in B cells, part of which can be affinity matured. These organs, howe...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.25592
更新日期:2013-09-01 00:00:00
abstract::Tandem single-chain variable fragment (scFv) bispecific antibodies (bsAb) are one of the most promising bsAb formats reported thus far. Yet, because of their increased aggregation propensity, high impurity content due to low expression level, smaller size and lack of the Fc region, it is challenging to isolate these p...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2020.1718440
更新日期:2020-01-01 00:00:00
abstract::Pharmacokinetic (PK) testing of a humanized (κI, VH3 framework) and affinity matured anti-hepatitis C virus E2-glycoprotein (HCV-E2) antibody (hu5B3.κ1VH3.v3) in rats revealed unexpected fast clearance (34.9 mL/day/kg). This antibody binds to the rat recycling receptor FcRn as expected for a human IgG1 antibody and do...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.29809
更新日期:2014-01-01 00:00:00
abstract::The Fc glycosylation of therapeutic antibodies is crucial for their effector functions and their behavior in pharmacokinetics and pharmacodynamics. To monitor the Fc glycosylation in bioprocess development and characterization,high-throughput techniques for glycosylation analysis are needed. Here, we describe the deve...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.26712
更新日期:2014-01-01 00:00:00
abstract::A mono-specific antibody may recruit a second antigen binding specificity, thus converting to a dual-specific Two-in-One antibody through mutation at the light chain complementarity-determining regions (CDRs). It is, however, unknown whether mutation at the heavy chain CDRs may evolve such dual specificity. Herein, we...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.28483
更新日期:2014-05-01 00:00:00
abstract::Although extensively studied, protein-protein interactions remain highly elusive and are of increasing interest in drug development. We show the assembly of a monoclonal antibody, using multivalent carboxylate ions, into highly-ordered structures. While the presence and function of similar structures in vivo are not k...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.23183
更新日期:2013-03-01 00:00:00
abstract::The critical role played by IgE in allergic asthma is well-documented and clinically precedented, but some patients in whom IgE neutralization may still offer clinical benefit are excluded from treatment with the existing anti-IgE therapy, omalizumab, due to high total IgE levels or body mass. In this study, we sought...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.28394
更新日期:2014-05-01 00:00:00
abstract::Surface and interfacial adsorption of antibody molecules could cause structural unfolding and desorbed molecules could trigger solution aggregation, resulting in the compromise of physical stability. Although antibody adsorption is important and its relevance to many mechanistic processes has been proposed, few techni...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2016.1276141
更新日期:2017-04-01 00:00:00
abstract::One aspiration for the formulation of human monoclonal antibodies (mAb) is to reach high solution concentrations without compromising stability. Protein surface activity leading to instability is well known, but our understanding of mAb adsorption to the solid-liquid interface in relevant pH and surfactant conditions ...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.22522
更新日期:2013-01-01 00:00:00
abstract::Ricin is a toxin that could potentially be used as a bioweapon. We identified anti-ricin A chain antibodies by sequencing the antibody repertoire from immunized mice and by selecting high affinity antibodies using yeast surface display. These methods led to the isolation of multiple antibodies with high (sub-nanomolar...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2016.1190059
更新日期:2016-08-01 00:00:00
abstract::Immunotherapy approaches for Alzheimer disease currently are among the leading therapeutic directions for the disease. Active and passive immunotherapy against the beta-amyloid peptides that aggregate and accumulate in the brain of those afflicted by the disease have been shown by numerous groups to reduce plaque path...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.1.2.7829
更新日期:2009-03-01 00:00:00
abstract::Ch-mAb7F9, a human-mouse chimeric monoclonal antibody (mAb) designed to bind (+)-methamphetamine (METH) with high affinity and specificity, was produced as a treatment medication for METH abuse. In these studies, we present the preclinical characterization that provided predictive evidence that ch-mAb7F9 may be safe a...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.27620
更新日期:2014-03-01 00:00:00
abstract::The development and production of recombinant monoclonal antibodies is well established. Although most of these are IgGs, there is also great interest in producing recombinant IgAs since this isotype plays a critical role in providing immunologic protection at mucosal surfaces. The choice of expression system for prod...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.2.3.11802
更新日期:2010-05-01 00:00:00
abstract::We describe here the identification of a stop codon TAA (Stop) → GAA (Glu) = Stop221E mutation on the light chain of a recombinant IgG1 antibody expressed in a Chinese hamster ovary (CHO) cell line. The extended light chain variants, which were caused by translation beyond the mutated stop codon to the next alternativ...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.22232
更新日期:2012-11-01 00:00:00
abstract::Fusion to an IgG Fc region is an established strategy to extend the half-life of therapeutic proteins. Most Fc fusion proteins, however, do not achieve the long half-life of IgGs. Based on findings that scFv-Fc fusion proteins exhibit a shorter half-life than the corresponding IgG molecules, we performed a comparative...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2015.1113360
更新日期:2016-01-01 00:00:00