A Reappraisal of Sedimentation Nonideality Coefficients for the Analysis of Weak Interactions of Therapeutic Proteins

The AAPS Journal
Sumit K Chaturvedi, Peter Schuck

Abstract

The study of weak or colloidal interactions of therapeutic proteins in different formulations allows prediction and optimization of protein stability. Various biophysical techniques have been applied to determine the second osmotic virial coefficient B2 as it reflects on the macromolecular distance distribution that governs solution behavior at high concentration. In the present work, we exploit a direct link predicted by hydrodynamic theory between B2 and the nonideality of sedimentation, commonly measured in sedimentation velocity analytical ultracentrifugation through the nonideality coefficient of sedimentation, kS. Using sedimentation equilibrium analytical ultracentrifugation for independent measurement of B2, we have examined the dependence of kS on B2 for model proteins in different buffers. The data exhibit the expected linear relationship and highlight the impact of protein shape on the magnitude of the nonideality coefficient kS. Recently, measurements of kS have been considerably simplified allowing higher throughput and simultaneous polydispersity assessment at higher protein concentrations. Thus, sedimentation velocity may offer a useful approach to compare the impact of formulation conditions on weak interactions...Continue Reading

References

Nov 1, 1992·Analytical Biochemistry·M L Johnson
Nov 1, 1985·The Biochemical Journal·S E Harding, P Johnson
Oct 1, 1972·Biophysical Journal·W F Stafford, D A Yphantis
Jul 22, 1965·Biochimica Et Biophysica Acta·J M Creeth, C G Knight
Sep 22, 2000·Analytical Biochemistry·S R KarP Schuck
Feb 28, 2002·Biophysical Journal·Peter M TessierStanley I Sandler
May 5, 2004·Journal of Pharmaceutical Sciences·Steven J ShireJun Liu
Oct 4, 2005·Biophysical Journal·Joseph J ValenteCharles S Henry
Dec 24, 2008·Analytical Biochemistry·Rachel R Kroe, Thomas M Laue
Apr 7, 2010·Physical Review Letters·A Moncho-JordáJ T Padding
Apr 24, 2010·Nature Reviews. Immunology·Alain BeckNathalie Corvaia
Jul 2, 2010·Macromolecular Bioscience·Shirley Ang, Arthur J Rowe
Nov 30, 2010·Methods : a Companion to Methods in Enzymology·Germán Rivas, Allen P Minton
Feb 5, 2011·Journal of Pharmaceutical Sciences·Christian LehermayrStefan Fischer
Oct 4, 2011·Biophysical Journal·Shantanu V SulePeter M Tessier
Sep 1, 2014·Current Opinion in Biotechnology·Christopher J Roberts
Oct 10, 2014·Nature Biotechnology·Gary Walsh
Aug 12, 2015·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·A Quigley, D R Williams
Mar 2, 2016·Journal of Pharmaceutical Sciences·Ranendu GhoshChristopher J Roberts
Mar 29, 2016·Molecular Pharmaceutics·Ashlesha S Raut, Devendra S Kalonia
Jun 18, 2016·The Journal of Physical Chemistry. B·Cesar Calero-RubioChristopher J Roberts
Aug 16, 2016·PloS One·Abhiksha DesaiPeter Schuck
Nov 30, 2016·Journal of Pharmaceutical Sciences·Teddy J ZbacnikMark Cornell Manning
Jan 11, 2017·MAbs·Ulrich Brinkmann, Roland E Kontermann

❮ Previous
Next ❯

Citations

Mar 20, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Aleksandra PorębskaPiotr Dobryszycki
Sep 8, 2019·Analytical Biochemistry·Kristian Juul-MadsenPeter Schuck
Aug 7, 2019·Langmuir : the ACS Journal of Surfaces and Colloids·Maximilian J UttingerWolfgang Peukert

❮ Previous
Next ❯

Methods Mentioned

BETA
static light scattering
light scattering

Software Mentioned

SEDPHAT
SEDFIT
MATLAB

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.