title: Bioconjugation of Serum Albumin to a Maleimide-appended Porphyrin/Cyclodextrin Supramolecular Complex as an Artificial Oxygen Carrier in the Bloodstream.
abstract: HemoCD is an inclusion complex of per-O-methylated β-cyclodextrin dimer and an iron(II) porphyrin, which forms a stable O2 complex in water. Therefore, hemoCD has the potential for use as a synthetic O2 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 O2 carrier. The O2 -binding affinities (P1/2 [Torr]) and half-lives (t1/2 [h]) of the O2 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.
authors.affiliation: Department of Molecular Chemistry and Biochemistry, Faculty of Science and Engineering, Doshisha University, 1-3 Tatara Miyakodani, Kyotanabe, Kyoto 610-0321, Japan. hkitagis@mail.doshisha.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kitagishi
authors.affiliation: Department of Molecular Chemistry and Biochemistry, Faculty of Science and Engineering, Doshisha University, 1-3 Tatara Miyakodani, Kyotanabe, Kyoto 610-0321, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawasaki
authors.affiliation: Department of Molecular Chemistry and Biochemistry, Faculty of Science and Engineering, Doshisha University, 1-3 Tatara Miyakodani, Kyotanabe, Kyoto 610-0321, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kano
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000737:chemistry* / Q000493:pharmacokinetics; D003505:Cyclodextrins / Q000737:chemistry* / Q000493:pharmacokinetics; D019281:Dimerization; D008297:Male; D008301:Maleimides / Q000737:chemistry* / Q000493:pharmacokinetics; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry* / Q000493:pharmacokinetics; D011166:Porphyrins / Q000737:chemistry* / Q000493:pharmacokinetics; D017208:Rats, Wistar; D012709:Serum Albumin / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D001802:Blood Substitutes; D003505:Cyclodextrins; D008301:Maleimides; D011166:Porphyrins; D012709:Serum Albumin; C043592:maleimide; D010100:Oxygen
keywords: cyclodextrins; oxygen; porphyrinoids; protein modifications; supramolecular chemistry