Journal
BIOCHEMISTRY
Volume 55, Issue 20, Pages 2875-2882Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.biochem.6b00215
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Funding
- Canadian Blood Services
- Ontario Graduate Scholarship
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Hypertension resulting from vasoconstriction in clinical trials of cross-linked tetrameric (alpha(2)beta(2)) human hemoglobins implicates the extravasation of the hemoglobins into endothelia where they scavenge nitric oxide (NO), which is the signal for relaxation of the surrounding smooth muscle. Thus, we sought an efficient route to create a larger species that avoids extravasation while maintaining the oxygenation function of hemoglobin. Selectively formed cysteine-linked biotin conjugates of hemoglobin undergo self-assembly with avidin into a stable triple protein, hemoglobin-avidin-hemoglobin (HbAvHb), which binds and releases oxygen with moderate affinity and cooperativity. The triple protein is likely to be stabilized by interactions of each constituent hemoglobin (pI 6.9) with the oppositely charged avidin (pI 10.5) as well as the strong association of the biotin moieties on hemoglobin with avidin.
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