Journal Article

FZJ-2021-03880

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Molecular Flexibility of Antibodies Preserved Even in the Dense Phase after Macroscopic Phase Separation

Girelli, A. ; Beck, C. ; Bäuerle, F. ; Matsarskaia, O. ; Maier, R. ; Zhang, F. ; Wu, B.FZJ* ; Lang, C.FZJ* ; Czakkel, O. ; Seydel, T. ; Schreiber, F. ; Roosen-Runge, F. (Corresponding author)

2021
American Chemical Society Washington, DC

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Please use a persistent id in citations: http://hdl.handle.net/2128/29020  doi:10.1021/acs.molpharmaceut.1c00555

Abstract: Antibody therapies are typically based on high-concentration formulations that need to be administered subcutaneously. These conditions induce several challenges, inter alia a viscosity suitable for injection, sufficient solution stability, and preservation of molecular function. To obtain systematic insights into the molecular factors, we study the dynamics on the molecular level under strongly varying solution conditions. In particular, we use solutions of antibodies with poly(ethylene glycol), in which simple cooling from room temperature to freezing temperatures induces a transition from a well-dispersed solution into a phase-separated and macroscopically arrested system. Using quasi-elastic neutron scattering during in situ cooling ramps and in prethermalized measurements, we observe a strong decrease in antibody diffusion, while internal flexibility persists to a significant degree, thus ensuring the movement necessary for the preservation of molecular function. These results are relevant for a more dynamic understanding of antibodies in high-concentration formulations, which affects the formation of transient clusters governing the solution viscosity.

Keyword(s): Polymers, Soft Nano Particles and Proteins (1st) ; Chemistry (2nd) ; Soft Condensed Matter (2nd)

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Contributing Institute(s):

1. JCNS-4 (JCNS-4)
2. Neutronenstreuung (JCNS-1)
3. JCNS-FRM-II (JCNS-FRM-II)
4. Heinz Maier-Leibnitz Zentrum (MLZ)

Research Program(s):

1. 6G4 - Jülich Centre for Neutron Research (JCNS) (FZJ) (POF4-6G4) (POF4-6G4)
2. 632 - Materials – Quantum, Complex and Functional Materials (POF4-632) (POF4-632)

Experiment(s):

1. KWS-2: Small angle scattering diffractometer (NL3ao)
2. KWS-3: Very small angle scattering diffractometer with focusing mirror (NL3auS)

Appears in the scientific report 2021

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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