Document Type
Article
Publication Date
4-20-2020
Keywords
JMG
JAX Source
Commun Biol 2020 Apr 20; 3(1):181
Volume
3
Issue
1
First Page
181
Last Page
181
ISSN
2399-3642
PMID
32313072
DOI
https://doi.org/10.1038/s42003-020-0903-7
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.
Recommended Citation
Nilsen J,
Trabjerg E,
Grevys A,
Azevedo C,
Brennan S,
Stensland M,
Wilson J,
Sand K,
Bern M,
Dalhus B,
Roopenian DC,
Sandlie I,
Rand K,
Andersen J.
An intact C-terminal end of albumin is required for its long half-life in humans. Commun Biol 2020 Apr 20; 3(1):181
Comments
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