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000901872 1001_ $$0P:(DE-HGF)0$$aGirelli, Anita$$b0
000901872 245__ $$aMolecular Flexibility of Antibodies Preserved Even in the Dense Phase after Macroscopic Phase Separation
000901872 260__ $$aWashington, DC$$bAmerican Chemical Society$$c2021
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000901872 520__ $$aAntibody 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.
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000901872 65017 $$0V:(DE-MLZ)GC-1602-2016$$2V:(DE-HGF)$$aPolymers, Soft Nano Particles and  Proteins$$x0
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000901872 7001_ $$00000-0001-7214-3447$$aBeck, Christian$$b1
000901872 7001_ $$0P:(DE-HGF)0$$aBäuerle, Famke$$b2
000901872 7001_ $$00000-0002-7293-7287$$aMatsarskaia, Olga$$b3
000901872 7001_ $$00000-0003-3428-039X$$aMaier, Ralph$$b4
000901872 7001_ $$00000-0001-7639-8594$$aZhang, Fajun$$b5
000901872 7001_ $$0P:(DE-Juel1)151161$$aWu, Baohu$$b6$$ufzj
000901872 7001_ $$0P:(DE-Juel1)168105$$aLang, Christian$$b7
000901872 7001_ $$0P:(DE-HGF)0$$aCzakkel, Orsolya$$b8
000901872 7001_ $$00000-0001-9630-1630$$aSeydel, Tilo$$b9
000901872 7001_ $$00000-0003-3659-6718$$aSchreiber, Frank$$b10
000901872 7001_ $$00000-0001-5106-4360$$aRoosen-Runge, Felix$$b11$$eCorresponding author
000901872 773__ $$0PERI:(DE-600)2132489-X$$a10.1021/acs.molpharmaceut.1c00555$$gp. acs.molpharmaceut.1c00555$$n11$$p4162–4169$$tMolecular pharmaceutics$$v18$$x1543-8392$$y2021
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