A New Polyethyleneglycol-Derivatized Hemoglobin Derivative with Decreased Oxygen Affinity and Limited Toxicity.
Summary of "A New Polyethyleneglycol-Derivatized Hemoglobin Derivative with Decreased Oxygen Affinity and Limited Toxicity."
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.
Affiliation
Department of Chemistry and Chemical Enginering, Babes-Bolyai University, 11 Arany Janos street, Cluj-Napoca, Romania.
Journal Details
This article was published in the following journal.
Name: The protein journal
ISSN: 1875-8355
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21161348
- DOI: http://dx.doi.org/10.1007/s10930-010-9298-5
Medical and Biotech [MESH] Definitions
2,3-diphosphoglycerate
A highly anionic organic phosphate which is present in human red blood cells at about the same molar ratio as hemoglobin. It binds to deoxyhemoglobin but not the oxygenated form, therefore diminishing the oxygen affinity of hemoglobin. This is essential in enabling hemoglobin to unload oxygen in tissue capillaries. It is also an intermediate in the conversion of 3-phosphoglycerate to 2-phosphoglycerate by phosphoglycerate mutase (EC 5.4.2.1). (From Stryer Biochemistry, 4th ed, p160; Enzyme Nomenclature, 1992, p508)
Carbon Monoxide
Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. (From Merck Index, 11th ed)
Oxyhemoglobins
A compound formed by the combination of hemoglobin and oxygen. It is a complex in which the oxygen is bound directly to the iron without causing a change from the ferrous to the ferric state.
Blood Substitutes
Substances that can carry oxygen to and carbon dioxide away from the tissues when introduced into the blood stream. They are used to replace hemoglobin in severe hemorrhage and also to perfuse isolated organs. The best known are perfluorocarbon emulsions and various hemoglobin solutions.
Leghemoglobin
A hemoglobin-like oxygen-binding hemeprotein present in the nitrogen-fixing root nodules of leguminous plants. The red pigment has a molecular weight approximately 1/4 that of hemoglobin and has been suggested to act as an oxido-reduction catalyst in symbiotic nitrogen fixation.
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