Hemoglobin-based oxygen carriers (HBOCs) are of great interest for their potential as
a safer alternative to blood transfusions. To overcome the vasoactivity associated with
small HBOCs, our group is interested in connecting two hemoglobin tetramers together,
forming “bis-tetramers”. Bis-tetramers have previously been synthesized by our group,
but yield and purity of the resulting solutions have been low and hindered their usefulness for trials. A new cross-linker was designed in an attempt to improve yield. This thesis describes the synthesis of an acyl phosphate cross-linker N-[bis(sodium methyl phosphate)isophthalyl]-4-azidomethylbenzoate (5), its modification of hemoglobin and subsequent purification attempts of the resulting solution. Cross-linker 5 was found to be selective to β-β-crosslinking and produced singly modified subunits as byproducts.
Attempts to purify the resulting reaction mixture by heating resulted in the decomposition of the azide group on the cross-linker, which was critical for the coupling step. Efforts to overcome this problem were unsuccessful.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/33587 |
| Date | 27 November 2012 |
| Creators | Wilson, Elizabeth |
| Contributors | Kluger, Ronald |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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