TY - JOUR
T1 - Role of extension arm in PEG-Hb conjugates on the stability of the tetramer
T2 - Non-conservative EAF maleimide thio-PEG mediated PEGylation
AU - Ananda, K.
AU - Acharya, Seetharama A.
N1 - Funding Information:
The authors of this paper would like to thank the National Institute of Health for its financial support by Grants HL71064 and HL58512. The authors of this article would like to thank Drs. Parimala Nacharaju, Tao Hu, Dongxia Li, Fantao Meng, and Maria Lobo for their valuable comments and help in preparing this manuscript.
PY - 2008/12
Y1 - 2008/12
N2 - PEGylation induced increase in colloidal osmotic pressure (COP) of Hb, one of the unique molecular properties of PEG-Hb conjugates, facilitates the neutralization of the vasoconstrictive activity of acellular Hb is a function of chemistry of conjugation of PEG-chains. The dependence of COP with the chemistry is a consequence of PEGylation induced weakening of interdimeric interactions. The conservative Extension Arm Facilitated (EAF) PEGylation exerts least influence on lowering the tetramer stability as compared to direct PEGylation. We have now designed a new, non-conservative EAF PEGylation that uses acylation chemistry to introduce the extension arm onto proteins to delineate the role of the extension arm and of the charge at the site of attachment in PEG-Hb conjugate on tetramer stability. The non-conservative EAF PEGylation does not lower the tetramer stability just as the non-conservative direct PEGylation of Hb. The impact of the extension arm in PEGylated Hb in terms of their structure and potential significance of higher tetramer stability of PEG-Hb conjugates generated by EAF-PEGylation in the in vivo toxicity and in the design of oxygen carrying plasma expander has been discussed.
AB - PEGylation induced increase in colloidal osmotic pressure (COP) of Hb, one of the unique molecular properties of PEG-Hb conjugates, facilitates the neutralization of the vasoconstrictive activity of acellular Hb is a function of chemistry of conjugation of PEG-chains. The dependence of COP with the chemistry is a consequence of PEGylation induced weakening of interdimeric interactions. The conservative Extension Arm Facilitated (EAF) PEGylation exerts least influence on lowering the tetramer stability as compared to direct PEGylation. We have now designed a new, non-conservative EAF PEGylation that uses acylation chemistry to introduce the extension arm onto proteins to delineate the role of the extension arm and of the charge at the site of attachment in PEG-Hb conjugate on tetramer stability. The non-conservative EAF PEGylation does not lower the tetramer stability just as the non-conservative direct PEGylation of Hb. The impact of the extension arm in PEGylated Hb in terms of their structure and potential significance of higher tetramer stability of PEG-Hb conjugates generated by EAF-PEGylation in the in vivo toxicity and in the design of oxygen carrying plasma expander has been discussed.
KW - Acylation
KW - Blood substitutes
KW - Colloidal osmotic pressure
KW - Hemoglobin
KW - PEGylation
UR - http://www.scopus.com/inward/record.url?scp=58149097515&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58149097515&partnerID=8YFLogxK
U2 - 10.1080/10731190802554133
DO - 10.1080/10731190802554133
M3 - Article
C2 - 19085194
AN - SCOPUS:58149097515
SN - 1073-1199
VL - 36
SP - 499
EP - 512
JO - Artificial Cells, Blood Substitutes, and Biotechnology
JF - Artificial Cells, Blood Substitutes, and Biotechnology
IS - 6
ER -