Differences in conformational stability between native and phosphorylated acetylcholinesterase as evidenced by a monoclonal antibody

Biochemistry ◽  
1990 ◽  
Vol 29 (10) ◽  
pp. 2456-2463 ◽  
Author(s):  
Yacov Ashani ◽  
Mary K. Gentry ◽  
Bhupendra P. Doctor
Keyword(s):  
Monoclonal Antibody ◽  
Conformational Stability

Local Dynamics and Their Alteration by Excipients Modulate the Global Conformational Stability of an lgG1 Monoclonal Antibody

2012 ◽  
Vol 101 (12) ◽  
pp. 4444-4457 ◽  
Author(s):  
Santosh V. Thakkar ◽  
Jae Hyun Kim ◽  
Hardeep S. Samra ◽  
Hasige A. Sathish ◽  
Steven M. Bishop ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Conformational Stability ◽  
Local Dynamics

Effects of Salts from the Hofmeister Series on the Conformational Stability, Aggregation Propensity, and Local Flexibility of an IgG1 Monoclonal Antibody

Biochemistry ◽  
2013 ◽  
Vol 52 (19) ◽  
pp. 3376-3389 ◽  
Author(s):  
Ranajoy Majumdar ◽  
Prakash Manikwar ◽  
John M. Hickey ◽  
Hardeep S. Samra ◽  
Hasige A. Sathish ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Conformational Stability ◽  
Hofmeister Series ◽  
Aggregation Propensity ◽  
Igg1 Monoclonal Antibody ◽  
Local Flexibility

scholarly journals Simultaneous High-Throughput Conformational and Colloidal Stability Screening Using a Fluorescent Molecular Rotor Dye, 4-(4-(Dimethylamino)styryl)-N-Methylpyridinium Iodide (DASPMI)

2016 ◽  
Vol 21 (8) ◽  
pp. 842-850 ◽  
Author(s):  
Jensen J. H. Wong ◽  
Sara K. Wright ◽  
Irene Ghozalli ◽  
Rajni Mehra ◽  
Kenji Furuya ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Colloidal Stability ◽  
Conformational Stability ◽  
Protein Structures ◽  
Tween 80 ◽  
Molecular Rotor ◽  
Formulation Development ◽  
Scanning Calorimetry ◽  
Dsc Measurements ◽  
Early Formulation

Technologies to improve the throughput for screening protein formulations are continuously evolving. The purpose of this article is to highlight novel applications of a molecular rotor dye, 4-(4-(dimethylamino)styryl)- N-methylpyridinium iodide (DASPMI) in screening for the conformational stability, colloidal stability, and subtle pretransition dynamics of protein structures during early formulation development. The measurement of the apparent unfolding temperature (Tm) for a monoclonal antibody in the presence of Tween 80 was conducted and data were compared to the results of differential scanning calorimetry (DSC) measurements. Additionally, measuring the fluorescence intensity of DASPMI as a function of protein concentration shows consistent correlation to the diffusion interaction parameter (kD) for two distinct monoclonal antibody formulations measured by DLS. Lastly, due to the sensitivity of the molecular rotor dye to changes in microviscosity (ηmicro), subtle pretransition dynamics were discernable for two monoclonal antibody formulations that correlate with findings by red-edge excitation shift (REES) experiments. This novel application of molecular rotor dyes offers a valuable and promising approach for streamlining the early formulation development process due to low material consumption and rapid analysis time in a 96-well plate format.

scholarly journals High-Throughput Biophysical Analysis and Data Visualization of Conformational Stability of an IgG1 Monoclonal Antibody After Deglycosylation

2013 ◽  
Vol 102 (11) ◽  
pp. 3942-3956 ◽  
Author(s):  
Mohammad A. Alsenaidy ◽  
Jae Hyun Kim ◽  
Ranajoy Majumdar ◽  
David D. Weis ◽  
Sangeeta B. Joshi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Data Visualization ◽  
High Throughput ◽  
Conformational Stability ◽  
Igg1 Monoclonal Antibody ◽  
Biophysical Analysis

scholarly journals Mimotopes of Apical Membrane Antigen 1: Structures of Phage-Derived Peptides Recognized by the Inhibitory Monoclonal Antibody 4G2dc1 and Design of a More Active Analogue

2006 ◽  
Vol 75 (1) ◽  
pp. 61-73 ◽  
Author(s):  
Jennifer K. Sabo ◽  
David W. Keizer ◽  
Zhi-Ping Feng ◽  
Joanne L. Casey ◽  
Kathy Parisi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Phage Display ◽  
Apical Membrane ◽  
Consensus Sequence ◽  
Conformational Stability ◽  
Resonance Spectroscopy ◽  
Merozoite Invasion ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen

ABSTRACT Apical membrane antigen 1 (AMA1) of the malaria parasite Plasmodium falciparum is an integral membrane protein that plays a key role in merozoite invasion of host erythrocytes. A monoclonal antibody, 4G2dc1, recognizes correctly folded AMA1 and blocks merozoite invasion. Phage display was used to identify peptides that bind to 4G2dc1 and mimic an important epitope of AMA1. Three of the highest-affinity binders—J1, J3, and J7—were chosen for antigenicity and immunogenicity studies. J1 and J7 were found to be true antigen mimics since both peptides generated inhibitory antibodies in rabbits (J. L. Casey et al., Infect. Immun. 72:1126-1134, 2004). In the present study, the solution structures of all three mimotopes were investigated by nuclear magnetic resonance spectroscopy. J1 adopted a well-defined region of structure, which can be attributed in part to the interactions of Trp11 with surrounding residues. In contrast, J3 and J7 did not adopt an ordered conformation over the majority of residues, although they share a region of local structure across their consensus sequence. Since J1 was the most structured of the peptides, it provided a template for the design of a constrained analogue, J1cc, which shares a structure similar to that of J1 and has a disulfide-stabilized conformation around the Trp11 region. J1cc binds with greater affinity to 4G2dc1 than does J1. These peptide structures provide the foundation for a better understanding of the complex conformational nature of inhibitory epitopes on AMA1. With its greater conformational stability and higher affinity for AMA1, J1cc may be a better in vitro correlate of immunity than the peptides identified by phage display.

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