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Bioconjugation of Serum Albumin to a Maleimide‐appended Porphyrin/Cyclodextrin Supramolecular Complex as an Artificial Oxygen Carrier in the Bloodstream
Author(s) -
Kitagishi Hiroaki,
Kawasaki Hiroki,
Kano Koji
Publication year - 2015
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201500451
Subject(s) - chemistry , porphyrin , bioconjugation , maleimide , serum albumin , conjugated system , albumin , heme , adduct , cyclodextrin , stereochemistry , medicinal chemistry , polymer chemistry , combinatorial chemistry , photochemistry , organic chemistry , biochemistry , enzyme , polymer
HemoCD is an inclusion complex of per‐ O ‐methylated β‐cyclodextrin dimer and an iron(II) porphyrin, which forms a stable O 2 complex in water. Therefore, hemoCD has the potential for use as a synthetic O 2 carrier in mammalian blood. In this study, a hemoCD derivative having a maleimide group (Mal‐hemoCD) was conjugated to a Cys residue of serum albumin via a Michael addition reaction in order to increase the circulation time of the O 2 carrier. The O 2 ‐binding affinities ( P 1/2 [Torr]) and half‐lives ( t 1/2 [h]) of the O 2 adducts at pH 7.4 and 25 °C were determined to be 9 Torr and 23 h for Mal‐hemoCD, and 10 Torr and 14 h for albumin‐conjugated hemoCD (Alb‐hemoCD). Our pharmacokinetic study revealed that renal excretion of Alb‐hemoCD was effectively suppressed and that half of injected Alb‐hemoCD remained in blood at 3 h after injection. It is noteworthy that Mal‐hemoCD also had a long circulation time because of the bioconjugation reaction that occurred during circulation in the bloodstream.