Poly(ethylene glycol) Surface-Conjugated Apohemoglobin as a Synthetic Heme Scavenger.

Abstract

Apohemoglobin (apoHb) contains vacant hydrophobic heme-binding pockets that can bind to a variety of hydrophobic molecules. Thus, apoHb is a promising protein for drug delivery, bioimaging, and heme scavenging. Unfortunately, apoHb has a short half-life and precipitates at physiological temperature. In this study, apoHb was surface-conjugated with poly(ethylene glycol) (PEG) to improve the therapeutic potential of apoHb. The scalable PEGylation process had >95% protein yield with ∼10 to 12 PEGs attached to each apoHb αβ dimer. The resulting PEG-apoHb had an average molecular weight of ∼80 to 90 kDa and a hydrodynamic diameter of 11 nm. PEG-apoHb maintained high heme-binding affinity and 30-40% of the heme-binding activity. Moreover, heme-bound and heme-free PEG-apoHb bound to haptoglobin, enabling PEG-apoHb to potentially target CD163+ macrophages and monocytes. Finally, PEG-apoHb was stable at physiological temperature with minimal precipitation. In summary, the in vitro results shown demonstrate that PEG-apoHb could be an effective in vivo heme scavenger during states of hemolysis.

• Authors: Ivan S Pires, Chintan Savla, Andre F Palmer
• Journal: Biomacromolecules (Biomacromolecules) Vol. 21 Issue 6 Pg. 2155-2164 (06 08 2020) ISSN: 1526-4602 [Electronic] United States
• PMID: 32186855 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Apoproteins
• Hemoglobins
• apohemoglobin
• Polyethylene Glycols
• Heme

Topics

• Apoproteins
• Heme
• Hemoglobins
• Polyethylene Glycols