25. Engineering the Molecular Shape of PEG-Hemoglobin Adducts for Supraperfusion

  1. Andrea Mozzarelli3,4 and
  2. Stefano Bettati3,4
  1. Seetharama A. Acharya1,
  2. Marcos Intaglietta2,
  3. Amy G. Tsai2,
  4. Kulal Ananda1 and
  5. Fantao Meng1

Published Online: 4 JUL 2011

DOI: 10.1002/9781119975427.ch25

Chemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood

Chemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood

How to Cite

Acharya, S. A., Intaglietta, M., Tsai, A. G., Ananda, K. and Meng, F. (2011) Engineering the Molecular Shape of PEG-Hemoglobin Adducts for Supraperfusion, in Chemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood (eds A. Mozzarelli and S. Bettati), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9781119975427.ch25

Editor Information

  1. 3

    Department of Biochemistry and Molecular Biology, University of Parma, Parma, Italy

  2. 4

    National Institute of Biostructures and Biosystems, Rome, Italy

Author Information

  1. 1

    Departments of Medicine and of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY, USA

  2. 2

    Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA

Publication History

  1. Published Online: 4 JUL 2011
  2. Published Print: 12 AUG 2011

ISBN Information

Print ISBN: 9780470686683

Online ISBN: 9781119975427

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Keywords:

  • engineering molecular shape of PEG-hemoglobin adducts - for supraperfusion;
  • blood losses, corrected - using volume-restitution fluids (plasma expanders, PEs);
  • Enzon DecaPEGylated Bovine Hb - nonhypertensive;
  • PEGylation of bovine Hb - increasing O2 affinity;
  • thiolation-mediated EAF PEGylation of Hb - optimized for hexaPEGylation of oxy-Hb;
  • role of pattern of PEGylation and total PEG mass - conjugated to Hb on O2 to tissues;
  • PEGylation, targeted - to surface amino groups;
  • reductive PEGylation-induced weakening - of interdimeric interactions of tetrameric Hbs;
  • EAF HexaPEGylated Hb - a superperfusion agent;
  • EAF PEG-Hbs as mechanotransducers of e-NOS activity - and shear stress

Summary

This chapter contains sections titled:

  • Introduction

  • Enzon DecaPEGylated Bovine Hb is Nonhypertensive

  • EAF HexaPEGylated Hb (EAF P5K6-Hb) is Nonhypertensive

  • Molecular and Solution Properties of EAF HexaPEGylated Human Hb (EAF-P5K6-Hb)

  • High O2 Affinity of EAF HexaPEGylated Hb and Tissue Oxygenation in Extreme Hemodilution

  • Influence of Total PEG Mass Conjugated to Hb on O2 Affinity and Tissue Oxygenation by PEG-Hbs

  • Influence of PEGylation Chemistry on Structural, Functional, and Solution Properties of HexaPEGylated Hb

  • Reductive PEGylation-induced Weakening of Interdimeric Interactions of Tetrameric Hbs

  • PEGylation-promoted Dissociation of Hb Tetramer is Attenuated by the Extension Arms of EAF PEGylated Hbs

  • Does Urethane-linkage-mediated PEGylation of Hb Promote its Dissociation?

  • Hemospan: Prototype of EAF HexaPEGylated Hb Designed at Einstein

  • EAF HexaPEGylated Hb Compared to other Blood Substitutes of Earlier Designs

  • Reversible Protection of Cys-93(β) during EAF PEGylation of Hb and Crosslinked Hbs: A Structural Requirement to Generate Medium- and Low-O2-affinity PEG-Hbs

  • Engineering Extension Arms between the Protein Core and PEG Shell Attenuates PEGylation-promoted Tetramer Dissociation

  • Attenuation of Direct HexaPEGylation-promoted Dissociation of Hb Tetramers by Increasing the Tetramer Stability Through Chemical Modification

  • Influence of the Extension Arm on the HexaPEGylation-enhanced Thermal Stability of Hb

  • PEGylation of Hb Induces a Hydrostatic Molecular Drag to the PEG-Hb Conjugate

  • EAF HexaPEGylated Hb is a Superperfusion Agent

  • EAF PEG-Hb-induced Vasodilation

  • In vivo Vasodilation by EAF PEG-Hb through its Enhanced Nitrite Reductase Activity

  • EAF PEG-Hbs as Mechanotransducers of e-NOS Activity

  • The Pattern of PEGylation of Intramolecularly Crosslinked Hbs Influences the Viscosity of the PEG-Hb Solution

  • Conclusion

  • Acknowledgments

  • References