Albumin-neprilysin fusion protein: understanding stability using small angle X-ray scattering and molecular dynamic simulations

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Standard

Albumin-neprilysin fusion protein : understanding stability using small angle X-ray scattering and molecular dynamic simulations. / Kulakova, Alina; Indrakumar, Sowmya; Sønderby Tuelung, Pernille; Mahapatra, Sujata; Streicher, Werner W.; Peters, Günther H.J.; Harris, Pernille.

I: Scientific Reports, Bind 10, 10089, 2020.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Kulakova, A, Indrakumar, S, Sønderby Tuelung, P, Mahapatra, S, Streicher, WW, Peters, GHJ & Harris, P 2020, 'Albumin-neprilysin fusion protein: understanding stability using small angle X-ray scattering and molecular dynamic simulations', Scientific Reports, bind 10, 10089. https://doi.org/10.1038/s41598-020-67002-9

APA

Kulakova, A., Indrakumar, S., Sønderby Tuelung, P., Mahapatra, S., Streicher, W. W., Peters, G. H. J., & Harris, P. (2020). Albumin-neprilysin fusion protein: understanding stability using small angle X-ray scattering and molecular dynamic simulations. Scientific Reports, 10, [10089]. https://doi.org/10.1038/s41598-020-67002-9

Vancouver

Kulakova A, Indrakumar S, Sønderby Tuelung P, Mahapatra S, Streicher WW, Peters GHJ o.a. Albumin-neprilysin fusion protein: understanding stability using small angle X-ray scattering and molecular dynamic simulations. Scientific Reports. 2020;10. 10089. https://doi.org/10.1038/s41598-020-67002-9

Author

Kulakova, Alina ; Indrakumar, Sowmya ; Sønderby Tuelung, Pernille ; Mahapatra, Sujata ; Streicher, Werner W. ; Peters, Günther H.J. ; Harris, Pernille. / Albumin-neprilysin fusion protein : understanding stability using small angle X-ray scattering and molecular dynamic simulations. I: Scientific Reports. 2020 ; Bind 10.

Bibtex

@article{64a60c047ba04e2782dcbf2dae5c851c,
title = "Albumin-neprilysin fusion protein: understanding stability using small angle X-ray scattering and molecular dynamic simulations",
abstract = "Fusion technology is widely used in protein-drug development to increase activity, stability, and bioavailability of protein therapeutics. Fusion proteins, like any other type of biopharmaceuticals, need to remain stable during production and storage. Due to the high complexity and additional intramolecular interactions, it is not possible to predict the behavior of fusion proteins based on the behavior the individual proteins. Therefore, understanding the stability of fusion proteins on the molecular level is crucial for the development of biopharmaceuticals. The current study on the albumin-neprilysin (HSA-NEP) fusion protein uses a combination of thermal and chemical unfolding with small angle X-ray scattering and molecular dynamics simulations to show a correlation between decreasing stability and increasing repulsive interactions, which is unusual for most biopharmaceuticals. It is also seen that HSA-NEP is not fully flexible: it is present in both compact and extended conformations. Additionally, the volume fraction of each conformation changes with pH. Finally, the presence of NaCl and arginine increases stability at pH 6.5, but decreases stability at pH 5.0.",
author = "Alina Kulakova and Sowmya Indrakumar and {S{\o}nderby Tuelung}, Pernille and Sujata Mahapatra and Streicher, {Werner W.} and Peters, {G{\"u}nther H.J.} and Pernille Harris",
year = "2020",
doi = "10.1038/s41598-020-67002-9",
language = "English",
volume = "10",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Albumin-neprilysin fusion protein

T2 - understanding stability using small angle X-ray scattering and molecular dynamic simulations

AU - Kulakova, Alina

AU - Indrakumar, Sowmya

AU - Sønderby Tuelung, Pernille

AU - Mahapatra, Sujata

AU - Streicher, Werner W.

AU - Peters, Günther H.J.

AU - Harris, Pernille

PY - 2020

Y1 - 2020

N2 - Fusion technology is widely used in protein-drug development to increase activity, stability, and bioavailability of protein therapeutics. Fusion proteins, like any other type of biopharmaceuticals, need to remain stable during production and storage. Due to the high complexity and additional intramolecular interactions, it is not possible to predict the behavior of fusion proteins based on the behavior the individual proteins. Therefore, understanding the stability of fusion proteins on the molecular level is crucial for the development of biopharmaceuticals. The current study on the albumin-neprilysin (HSA-NEP) fusion protein uses a combination of thermal and chemical unfolding with small angle X-ray scattering and molecular dynamics simulations to show a correlation between decreasing stability and increasing repulsive interactions, which is unusual for most biopharmaceuticals. It is also seen that HSA-NEP is not fully flexible: it is present in both compact and extended conformations. Additionally, the volume fraction of each conformation changes with pH. Finally, the presence of NaCl and arginine increases stability at pH 6.5, but decreases stability at pH 5.0.

AB - Fusion technology is widely used in protein-drug development to increase activity, stability, and bioavailability of protein therapeutics. Fusion proteins, like any other type of biopharmaceuticals, need to remain stable during production and storage. Due to the high complexity and additional intramolecular interactions, it is not possible to predict the behavior of fusion proteins based on the behavior the individual proteins. Therefore, understanding the stability of fusion proteins on the molecular level is crucial for the development of biopharmaceuticals. The current study on the albumin-neprilysin (HSA-NEP) fusion protein uses a combination of thermal and chemical unfolding with small angle X-ray scattering and molecular dynamics simulations to show a correlation between decreasing stability and increasing repulsive interactions, which is unusual for most biopharmaceuticals. It is also seen that HSA-NEP is not fully flexible: it is present in both compact and extended conformations. Additionally, the volume fraction of each conformation changes with pH. Finally, the presence of NaCl and arginine increases stability at pH 6.5, but decreases stability at pH 5.0.

U2 - 10.1038/s41598-020-67002-9

DO - 10.1038/s41598-020-67002-9

M3 - Journal article

C2 - 32572086

AN - SCOPUS:85086773459

VL - 10

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 10089

ER -

ID: 249864509