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
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