PMID- 24641771
OWN - NLM
STAT- MEDLINE
DCOM- 20150903
LR  - 20181202
IS  - 2169-141X (Electronic)
IS  - 2169-1401 (Linking)
VI  - 43
IP  - 1
DP  - 2015 Feb
TI  - CO binding improves the structural, functional, physical and anti-oxidation 
      properties of the PEGylated hemoglobin.
PG  - 18-25
LID - 10.3109/21691401.2014.885444 [doi]
AB  - CONTEXT: PEGylated hemoglobin (Hb) is a promising oxygen therapeutic agent for 
      clinical application. However, it suffered from structural perturbation, 
      functional instability and methemoglobin (metHb) formation. OBJECTIVE: To improve 
      the structural, functional, physical and anti-oxidation properties of the 
      PEGylated Hb. MATERIALS AND METHODS: PEGylation of Hb with CO binding (HbCO) was 
      conducted using maleimide and acylation chemistry, respectively. Physical and 
      chemical parameters were measured for Hb samples. The circular dichroism spectra, 
      dynamic light scattering and analytical ultracentrifugation were used to 
      investigate the structure and conformation of PEGylated HbCO. RESULTS: CO binding 
      can inhibit the autoxidation of the PEGylated Hb, structurally stabilize its 
      tetramer and improve its thermal and pH stability. Importantly, the circular 
      dichroism spectra showed that CO binding can decrease the structural perturbation 
      of Hb induced by PEGylation. The PEGylated HbCO with CO release showed slightly 
      higher oxygen-delivery capacity than the PEGylated Hb. The PEGylated HbCO did not 
      show metHb formation after 30-day storage at 4 degrees C. DISCUSSION AND CONCLUSION: CO 
      binding structurally stabilized the PEGylated Hb, abolished its metHb formation, 
      and significantly increased its physical stability. In particular, it also 
      avoided the perturbation of PEG chains on the heme microenvironment. The 
      functional property of the PEGylated HbCO can be maintained during its long-term 
      storage, which is of great significance for field transfusion.
FAU - Wang, Qingqing
AU  - Wang Q
AD  - National Key Laboratory of Biochemical Engineering, Institute of Process 
      Engineering, Chinese Academy of Sciences , Beijing , P. R. China.
FAU - Hu, Tao
AU  - Hu T
FAU - Sun, Lijing
AU  - Sun L
FAU - Ji, Shaoyang
AU  - Ji S
FAU - Zhao, Dawei
AU  - Zhao D
FAU - Liu, Jiaxin
AU  - Liu J
FAU - Ma, Guanghui
AU  - Ma G
FAU - Su, Zhiguo
AU  - Su Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140319
PL  - England
TA  - Artif Cells Nanomed Biotechnol
JT  - Artificial cells, nanomedicine, and biotechnology
JID - 101594777
RN  - 0 (Blood Substitutes)
RN  - 0 (Hemoglobins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 7U1EE4V452 (Carbon Monoxide)
RN  - 9008-37-1 (Methemoglobin)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Blood Substitutes/*chemistry
MH  - Carbon Monoxide/*chemistry
MH  - Hemoglobins/*chemistry
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Methemoglobin/antagonists & inhibitors
MH  - Oxidation-Reduction
MH  - Oxygen/metabolism
MH  - Polyethylene Glycols/*chemistry
MH  - Protein Stability
OTO - NOTNLM
OT  - PEGylation
OT  - autoxidation
OT  - heme environment
OT  - oxygen carrier
OT  - thermal stability
EDAT- 2014/03/20 06:00
MHDA- 2015/09/04 06:00
CRDT- 2014/03/20 06:00
PHST- 2014/03/20 06:00 [entrez]
PHST- 2014/03/20 06:00 [pubmed]
PHST- 2015/09/04 06:00 [medline]
AID - 10.3109/21691401.2014.885444 [doi]
PST - ppublish
SO  - Artif Cells Nanomed Biotechnol. 2015 Feb;43(1):18-25. doi: 
      10.3109/21691401.2014.885444. Epub 2014 Mar 19.