Derivatization of haemoglobin with periodate-generated reticulation agents: evaluation of oxidative reactivity for potential blood substitutes.
Periodate modification of the sugar moiety in sugars, including adenosine triphosphate (ATP), has previously been employed in order to prepare dialdehyde-type reagents, which were then utilized in crosslinking reactions on haemoglobin, yielding polymerized material with useful dioxygen-binding properties and hence proposed as possible artificial oxygen carriers ('blood substitutes'). Here, the periodate protocol is shown to be applicable to a wider range of oxygen-containing compounds, illustrated by starch and polyethylene glycol. Derivatization protocols are described for haemoglobin with such periodate-treated crosslinking agents, and the dioxygen-binding properties and redox reactivities are investigated for the derivatized haemoglobins, with emphasis on pro-oxidative properties. There is a general tendency of the derivatization to result in higher autooxidation rates. The peroxide reactivity of the met (ferric) form is also affected by derivatization, as witnessed, among others, by varying yields of ferryl [Fe (IV)-oxo] and free radical generated. In cell, culture tests (human umbilical vein epithelial cells, HUVEC), the derivatization protocols show no toxic effect.
Department of Chemistry, Babes-Bolyai University, 11 Arany Janos street, Cluj-Napoca 40028, Romania.
Florina
F
Deac
Bianca
B
Iacob
Eva
E
Fischer-Fodor
Grigore
G
Damian
Radu
R
Silaghi-Dumitrescu
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D001802:Blood Substitutes / Q000737:chemistry*; D002417:Cattle; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D006454:Hemoglobins / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D008970:Molecular Weight; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D010504:Periodic Acid / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D058105:Polymerization; D013213:Starch / Q000737:chemistry; D014471:Umbilical Veins / Q000166:cytology
D001802:Blood Substitutes; D003432:Cross-Linking Reagents; D005609:Free Radicals; D006454:Hemoglobins; D010504:Periodic Acid; D011092:Polyethylene Glycols; C017199:2',3'-dialdehyde ATP; D000255:Adenosine Triphosphate; D013213:Starch; C009288:metaperiodate; D010100:Oxygen