title: Influence of Molecular Structure on O2-Binding Properties and Blood Circulation of Hemoglobin‒Albumin Clusters.
abstract: A hemoglobin wrapped covalently by three human serum albumins, a Hb-HSA3 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.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27, Kasuga, Bunkyo-ku, Tokyo, 112-8551, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27, Kasuga, Bunkyo-ku, Tokyo, 112-8551, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yokomaku
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27, Kasuga, Bunkyo-ku, Tokyo, 112-8551, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Haruki
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1, Ikeda, Nishi-ku, Kumamoto, 860-0082, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Nagao
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1, Ikeda, Nishi-ku, Kumamoto, 860-0082, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27, Kasuga, Bunkyo-ku, Tokyo, 112-8551, Japan.
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Komatsu
mesh_terms: D000818:Animals; D001775:Blood Circulation; D001802:Blood Substitutes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008297:Male; D015394:Molecular Structure; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D017208:Rats, Wistar; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D046912:Multiprotein Complexes; D012709:Serum Albumin; D010100:Oxygen