TY - JOUR
T1 - Influence of molecular structure on O2-binding properties and blood circulation of hemoglobin?albumin clusters
AU - Yamada, Kana
AU - Yokomaku, Kyoko
AU - Haruki, Risa
AU - Taguchi, Kazuaki
AU - Nagao, Saori
AU - Maruyama, Toru
AU - Otagiri, Masaki
AU - Komatsu, Teruyuki
N1 - Publisher Copyright:
© 2016 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/2
Y1 - 2016/2
N2 - A hemoglobin wrapped covalently by three human serum albumins, a Hb-HAS3 cluster, is an artificial O2-carrier with the potential to function as a red blood cell substitute. This paper describes the synthesis and O2-binding properties of new hemoglobin?albumin clusters(i) bearing four HSA units at the periphery(Hb-HSA4, large-size variant) and(ii) containing an intramolecularly crosslinked Hb in the center(XLHb-HSA3, high O2-affinity variant). Dynamic light scattering measurements revealed that the Hb-HSA4 diameter is greater than that of either Hb-HSA3 or XLHb-HSA3. The XLHb-HSA3 showed moderately high O2-affinity compared to the others because of the chemical linkage between the Cys-93(β) residues in Hb. Furthermore, the blood circulation behavior of 125I-labeled clusters was investigated by assay of blood retention and tissue distribution after intravenous administration into anesthetized rats. The XLHb-HSA3 was metabolized faster than Hb-HSA3 and Hb-HSA4. Results suggest that the molecular structure of the protein cluster is a factor that can influence in vivo circulation behavior.
AB - A hemoglobin wrapped covalently by three human serum albumins, a Hb-HAS3 cluster, is an artificial O2-carrier with the potential to function as a red blood cell substitute. This paper describes the synthesis and O2-binding properties of new hemoglobin?albumin clusters(i) bearing four HSA units at the periphery(Hb-HSA4, large-size variant) and(ii) containing an intramolecularly crosslinked Hb in the center(XLHb-HSA3, high O2-affinity variant). Dynamic light scattering measurements revealed that the Hb-HSA4 diameter is greater than that of either Hb-HSA3 or XLHb-HSA3. The XLHb-HSA3 showed moderately high O2-affinity compared to the others because of the chemical linkage between the Cys-93(β) residues in Hb. Furthermore, the blood circulation behavior of 125I-labeled clusters was investigated by assay of blood retention and tissue distribution after intravenous administration into anesthetized rats. The XLHb-HSA3 was metabolized faster than Hb-HSA3 and Hb-HSA4. Results suggest that the molecular structure of the protein cluster is a factor that can influence in vivo circulation behavior.
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U2 - 10.1371/journal.pone.0149526
DO - 10.1371/journal.pone.0149526
M3 - Article
C2 - 26895315
AN - SCOPUS:84960935946
SN - 1932-6203
VL - 11
JO - PLoS One
JF - PLoS One
IS - 2
M1 - e0149526
ER -