title: A new polyethyleneglycol-derivatized hemoglobin derivative with decreased oxygen affinity and limited toxicity.
abstract: A new protocol is described for derivatization of hemoglobin with polyethyleneglycol (PEG) via reaction of the unmodified native hemoglobin with an activated amine-reacting polyethylene glycol derivative which, unlike protocols previously described, leads to formation of a peptide bond between hemoglobin and PEG. Dioxygen binding and peroxide reactivities of the derivatized hemoglobin are examined, and found to be within reasonable limits, with the particular observation that, unlike with a few other derivatization protocols, the dioxygen affinity is slightly lower than that of native Hb. In cell culture tests (human umbilical vein epithelial cells, HUVEC), the derivatization protocol induces no toxic effect. These results show promise towards applicability for production of hemoglobin-based blood substitutes.
authors.affiliation: Department of Chemistry and Chemical Enginering, Babes-Bolyai University, 11 Arany Janos Street, Cluj-Napoca, Romania.
authors.forename: Oana
authors.initials: O
authors.lastname: Zolog
authors.forename: Augustin
authors.initials: A
authors.lastname: Mot
authors.forename: Florina
authors.initials: F
authors.lastname: Deac
authors.forename: Alina
authors.initials: A
authors.lastname: Roman
authors.forename: Eva
authors.initials: E
authors.lastname: Fischer-Fodor
authors.forename: Radu
authors.initials: R
authors.lastname: Silaghi-Dumitrescu
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity*; D002417:Cattle; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D010545:Peroxides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity; D014472:Umbilicus / Q000098:blood supply; D014680:Veins / Q000166:cytology
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D010545:Peroxides; D011092:Polyethylene Glycols; D006861:Hydrogen Peroxide; D010100:Oxygen