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MP4, a Vasodilatory PEGylated Hemoglobin

Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 701)

Abstract

A vasodilatory hemoglobin (Hb)-based O2 carrier (HBOC) has been developed by surface conjugation polyethylene glycol to tetrameric human Hb (MP4, Sangart, San Diego). Because the NO-binding kinetics of MP4 are similar to vasoconstrictiveHBOCs, we propose that the decoupling of NO scavenging from vascular response is a consequence of MP4’s high O2 affinity (p50 = 5 mmHg) and unique surface chemistry. The release of ATP from erythrocytes is vasodilatory and the application of a high O2 affinity HBOC minimizes ATP interference with intravascular ATP signaling. 1 A second potential mechanism of action for MP4 involves the surface conjugation of polyethylene glycol (PEG) to tetrameric human Hb. It has been shown that the addition of unconjugated high molecular weight (Mw) PEG to cultured lung endothelial cells causes an immediate and significant reduction in endothelial permeability; an effect opposite to that of endothelial agonists such as cell-free Hb. 2 It appears that some of the benefits of the PEG-endothelium interaction are carried onto molecules such as PEGylated Hb and PEGylated albumin, as demonstrated by favorable hemodynamic responses in vivo. PEGylation of ß93 cysteine residues, as in MP4, has also been reported to increase the nitrite reductase activity of Hb and enhance conversion of endogenous nitrite to bioactive NO.3

Keywords

Nitric Oxide Human Serum Albumin Mean Arterial Pressure Peripheral Vascular Resistance Functional Capillary Density 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Sangart Inc.San DiegoUSA

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