An intact C-terminal end of albumin is required for its long half-life in humans

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

An intact C-terminal end of albumin is required for its long half-life in humans. / Nilsen, Jeannette; Trabjerg, Esben; Grevys, Algirdas; Azevedo, Claudia; Brennan, Stephen O; Stensland, Maria; Wilson, John; Sand, Kine Marita Knudsen; Bern, Malin; Dalhus, Bjørn; Roopenian, Derry C; Sandlie, Inger; Rand, Kasper Dyrberg; Andersen, Jan Terje.

In: Communications Biology, Vol. 3, No. 1, 181, 20.04.2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Nilsen, J, Trabjerg, E, Grevys, A, Azevedo, C, Brennan, SO, Stensland, M, Wilson, J, Sand, KMK, Bern, M, Dalhus, B, Roopenian, DC, Sandlie, I, Rand, KD & Andersen, JT 2020, 'An intact C-terminal end of albumin is required for its long half-life in humans', Communications Biology, vol. 3, no. 1, 181. https://doi.org/10.1038/s42003-020-0903-7

APA

Nilsen, J., Trabjerg, E., Grevys, A., Azevedo, C., Brennan, S. O., Stensland, M., Wilson, J., Sand, K. M. K., Bern, M., Dalhus, B., Roopenian, D. C., Sandlie, I., Rand, K. D., & Andersen, J. T. (2020). An intact C-terminal end of albumin is required for its long half-life in humans. Communications Biology, 3(1), [181]. https://doi.org/10.1038/s42003-020-0903-7

Vancouver

Nilsen J, Trabjerg E, Grevys A, Azevedo C, Brennan SO, Stensland M et al. An intact C-terminal end of albumin is required for its long half-life in humans. Communications Biology. 2020 Apr 20;3(1). 181. https://doi.org/10.1038/s42003-020-0903-7

Author

Nilsen, Jeannette ; Trabjerg, Esben ; Grevys, Algirdas ; Azevedo, Claudia ; Brennan, Stephen O ; Stensland, Maria ; Wilson, John ; Sand, Kine Marita Knudsen ; Bern, Malin ; Dalhus, Bjørn ; Roopenian, Derry C ; Sandlie, Inger ; Rand, Kasper Dyrberg ; Andersen, Jan Terje. / An intact C-terminal end of albumin is required for its long half-life in humans. In: Communications Biology. 2020 ; Vol. 3, No. 1.

Bibtex

@article{e1b7ce4f98fc4bbc8362d4caf7619f62,
title = "An intact C-terminal end of albumin is required for its long half-life in humans",
abstract = "Albumin has an average plasma half-life of three weeks and is thus an attractive carrier to improve the pharmacokinetics of fused therapeutics. The half-life is regulated by FcRn, a cellular receptor that protects against intracellular degradation. To tailor-design the therapeutic use of albumin, it is crucial to understand how structural alterations in albumin affect FcRn binding and transport properties. In the blood, the last C-terminal residue (L585) of albumin may be enzymatically cleaved. Here we demonstrate that removal of the L585 residue causes structural stabilization in regions of the principal FcRn binding domain and reduces receptor binding. In line with this, a short half-life of only 3.5 days was measured for cleaved albumin lacking L585 in a patient with acute pancreatitis. Thus, we reveal the structural requirement of an intact C-terminal end of albumin for a long plasma half-life, which has implications for design of albumin-based therapeutics.",
author = "Jeannette Nilsen and Esben Trabjerg and Algirdas Grevys and Claudia Azevedo and Brennan, {Stephen O} and Maria Stensland and John Wilson and Sand, {Kine Marita Knudsen} and Malin Bern and Bj{\o}rn Dalhus and Roopenian, {Derry C} and Inger Sandlie and Rand, {Kasper Dyrberg} and Andersen, {Jan Terje}",
year = "2020",
month = apr,
day = "20",
doi = "10.1038/s42003-020-0903-7",
language = "English",
volume = "3",
journal = "Communications Biology",
issn = "2399-3642",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - An intact C-terminal end of albumin is required for its long half-life in humans

AU - Nilsen, Jeannette

AU - Trabjerg, Esben

AU - Grevys, Algirdas

AU - Azevedo, Claudia

AU - Brennan, Stephen O

AU - Stensland, Maria

AU - Wilson, John

AU - Sand, Kine Marita Knudsen

AU - Bern, Malin

AU - Dalhus, Bjørn

AU - Roopenian, Derry C

AU - Sandlie, Inger

AU - Rand, Kasper Dyrberg

AU - Andersen, Jan Terje

PY - 2020/4/20

Y1 - 2020/4/20

N2 - Albumin has an average plasma half-life of three weeks and is thus an attractive carrier to improve the pharmacokinetics of fused therapeutics. The half-life is regulated by FcRn, a cellular receptor that protects against intracellular degradation. To tailor-design the therapeutic use of albumin, it is crucial to understand how structural alterations in albumin affect FcRn binding and transport properties. In the blood, the last C-terminal residue (L585) of albumin may be enzymatically cleaved. Here we demonstrate that removal of the L585 residue causes structural stabilization in regions of the principal FcRn binding domain and reduces receptor binding. In line with this, a short half-life of only 3.5 days was measured for cleaved albumin lacking L585 in a patient with acute pancreatitis. Thus, we reveal the structural requirement of an intact C-terminal end of albumin for a long plasma half-life, which has implications for design of albumin-based therapeutics.

AB - Albumin has an average plasma half-life of three weeks and is thus an attractive carrier to improve the pharmacokinetics of fused therapeutics. The half-life is regulated by FcRn, a cellular receptor that protects against intracellular degradation. To tailor-design the therapeutic use of albumin, it is crucial to understand how structural alterations in albumin affect FcRn binding and transport properties. In the blood, the last C-terminal residue (L585) of albumin may be enzymatically cleaved. Here we demonstrate that removal of the L585 residue causes structural stabilization in regions of the principal FcRn binding domain and reduces receptor binding. In line with this, a short half-life of only 3.5 days was measured for cleaved albumin lacking L585 in a patient with acute pancreatitis. Thus, we reveal the structural requirement of an intact C-terminal end of albumin for a long plasma half-life, which has implications for design of albumin-based therapeutics.

U2 - 10.1038/s42003-020-0903-7

DO - 10.1038/s42003-020-0903-7

M3 - Journal article

C2 - 32313072

VL - 3

JO - Communications Biology

JF - Communications Biology

SN - 2399-3642

IS - 1

M1 - 181

ER -

ID: 239914591