Document Detail

Molecular aspects of the high oxygen affinity of non-hypertensive hexa pegylated hemoglobin, [(SP-PEG5K)(6)-Hb].
MedLine Citation:
PMID:  17364468     Owner:  NLM     Status:  MEDLINE    
The development of hexaPEGylated Hb, (SP-PEG5K)(6)-Hb, using the newly designed thiolation-mediated maleimide chemistry based PEGylation, has validated the concept that engineering 'plasma volume expander' -like properties to Hb neutralizes its vasoactivity. The high O(2) affinity of hexaPEGylated Hb has been attributed to the two PEG-5K chains on its two Cys-93(beta) residues. In an attempt to map the influence of the additional four PEG-5K chains of HexaPEGylated Hb on the O(2) affinity, we have now investigated the influence of PEGylation of the surface amino groups alone on the subunit interface interactions and O(2) affinity of Hb using rHb(betaC93A). The molecular radius of PEGylated rHb(betaC93A) was slightly smaller than that of (SP-PEG5K)(6)-Hb, and the overall site-selectivity of PEGylation in the PEGylated rHb(betaC93A) at Lys-residues was comparable to that of (SP-PEG5K)(6)-Hb. Proton NMR studies have shown that the conjugation of the protein with PEG-5K does not have any significant influence on its subunit interface interactions. Surprisingly, the influence of PEGylation on the O(2) affinity and Bohr effect of HbA and rHb(betaC93A) is also nearly the same. Apparently, conjugation of PEG-chains to Lys residues of Hb by the thiolation mediated PEGylation induces unique changes in the structure of the hydration shell of Hb (layer of tightly bound water molecules), which, in turn, induces constraints in its R to T conformational transition to favor the more hydrated R-state.
Dongxia Li; Belur N Manjula; Nancy T Ho; Virgil Simplaceanu; Chien Ho; A Seetharama Acharya
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Artificial cells, blood substitutes, and immobilization biotechnology     Volume:  35     ISSN:  1073-1199     ISO Abbreviation:  Artif Cells Blood Substit Immobil Biotechnol     Publication Date:  2007  
Date Detail:
Created Date:  2007-03-16     Completed Date:  2007-11-05     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  9431307     Medline TA:  Artif Cells Blood Substit Immobil Biotechnol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  19-29     Citation Subset:  IM    
Department of Physiology, Albert Einstein College of Medicine, Bronx, NY, USA.
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MeSH Terms
Binding Sites
Blood Pressure
Blood Substitutes / chemistry*
Hemoglobin A
Hemoglobins / chemistry*
Magnetic Resonance Spectroscopy
Oxygen / metabolism*
Polyethylene Glycols / chemistry*
Protein Conformation
Protein Subunits / chemistry
Grant Support
Reg. No./Substance:
0/Blood Substitutes; 0/Hemoglobins; 0/Polyethylene Glycols; 0/Protein Subunits; 56-87-1/Lysine; 7732-18-5/Water; 7782-44-7/Oxygen; 9034-51-9/Hemoglobin A

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