PMID- 29881837
OWN - NLM
STAT- MEDLINE
DCOM- 20181029
LR  - 20181202
IS  - 2047-4849 (Electronic)
IS  - 2047-4830 (Linking)
VI  - 6
IP  - 8
DP  - 2018 Jul 24
TI  - Comparative studies of the serum half-life extension of a protein via 
      site-specific conjugation to a species-matched or -mismatched albumin.
PG  - 2092-2100
LID - 10.1039/c8bm00456k [doi]
AB  - Human serum albumin (HSA) has been investigated as a serum half-life extender of 
      therapeutic proteins thanks to its unusually long serum half-life. However, in 
      mice, the serum half-life of a HSA-conjugated protein was much shorter than that 
      of HSA in humans, likely due to the species-dependent nature of albumin-FcRn 
      interactions. Herein, we investigated species-dependent albumin-FcRn interactions 
      using species-matched albumin (mouse serum albumin) and species-mismatched 
      albumin (HSA) in non-transgenic mice. We site-specifically introduced a clickable 
      non-natural amino acid to a target protein followed by conjugation to an albumin 
      species via a hetero-bifunctional linker. Using in vitro binding assays, we 
      showed that both HSA- and MSA-conjugated proteins bound mouse FcRns. Conjugation 
      of HSA led to very limited extension of the serum half-life of sfGFP in mice 
      (16.3 h), compared to that of HSA in transgenic mice harboring an allele of mouse 
      FcRn knock-out and expressing humn FcRn (67 h) reported previously. These results 
      suggest that the FcRn-mediated recycling of HSA is not effective in mice. 
      However, conjugation of mouse serum albumin (MSA) resulted in a serum half-life 
      of sfGFP (27.7 h) comparable to that of MSA in mice (28.8 h). Altogether, our 
      study supported that albumin-FcRn interactions are species dependent in vivo.
FAU - Yang, Byungseop
AU  - Yang B
AD  - School of Materials Science and Engineering, Gwangju Institute of Science and 
      Technology (GIST), 123 Cheomdan Gwagi-ro, Buk-gu, Gwangju, 61005, Republic of 
      Korea. inchan@gist.ac.kr.
FAU - Kim, Jong Chul
AU  - Kim JC
FAU - Seong, Jihyoun
AU  - Seong J
FAU - Tae, Giyoong
AU  - Tae G
FAU - Kwon, Inchan
AU  - Kwon I
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Biomater Sci
JT  - Biomaterials science
JID - 101593571
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Receptors, Fc)
RN  - 0 (Serum Albumin)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - TW3XAW0RCY (Fc receptor, neonatal)
SB  - IM
MH  - Animals
MH  - Green Fluorescent Proteins/*chemistry
MH  - Histocompatibility Antigens Class I/*chemistry
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Models, Molecular
MH  - Molecular Structure
MH  - Protein Binding
MH  - Receptors, Fc/*chemistry
MH  - Serum Albumin/*chemistry
EDAT- 2018/06/09 06:00
MHDA- 2018/10/30 06:00
CRDT- 2018/06/09 06:00
PHST- 2018/06/09 06:00 [pubmed]
PHST- 2018/10/30 06:00 [medline]
PHST- 2018/06/09 06:00 [entrez]
AID - 10.1039/c8bm00456k [doi]
PST - ppublish
SO  - Biomater Sci. 2018 Jul 24;6(8):2092-2100. doi: 10.1039/c8bm00456k.