Poly(ethylene glycol)-Conjugated Human Serum Albumin Including Iron Porphyrins: Surface Modification Improves the O2-Transporting Ability
作者：Yubin Huang, Teruyuki Komatsu, Rong-Min Wang, Akito Nakagawa,and Eishun Tsuchida
關鍵字：O2-Transporting Ability,Surface Modification
論文來源：期刊
具體來源：Bioconjugate Chem.
發(fā)表時間：2006年
Artificial O2-carrying hemoprotein composed of human serum albumin including tetrakis(o-amidophenyl)-
porphinatoiron(II) (Fe4P or Fe3P) [HSA-FeXP] has been modified by maleimide- or succinimide-terminated
poly(ethylene glycol) (PEG), and the formed PEG bioconjugates have been physicochemically characterized.
2-Iminothiolane (IMT) reacted with the amino groups of Lys to create active thiol groups, which bind to
R-maleimide-ö-methoxy PEG [Mw: 2-kDa (PEGM2), 5-kDa (PEGM5)]. On the other hand, R-succinimidyl-ö-
methoxy PEG [Mw: 2-kDa (PEGS2), 5-kDa (PEGS5)] directly binds to Lys residues. MALDI-TOF MS of the
PEG-conjugated HSA-FeXP showed distinct molecular ion peaks, which provide an accurate number of the
PEG chains. In the case of PEGMY(HSA-FeXP), the spectroscopic assay of the thiol groups also provided the
mean of the binding numbers of the polymers, and the degree of the modification was controlled by the ratio of
[IMT]/[HSA]. The viscosity and colloid osmotic pressures of the 2-kDa PEG conjugates (phosphate-buffered
saline solution, [HSA] ) 5 g dL-1) were almost the same as that of the nonmodified one, whereas the 5-kDa
PEG binding increased the rheological parameters. The presence of flexible polymers on the HSA surface retarded
the association reaction of O2 to FeXP and stabilized the oxygenated complex. Furthermore, PEGMY(HSAFeXP)
exhibited a long circulation lifetime of FeXP in rats (13-16 h). On the basis of these results, it can be
concluded that the surface modification of HSA-FeXP by PEG has improved its comprehensive O2-transporting
ability. In particular the PEGMY(HSA-FeXP) solution could be a promising material for entirely synthetic O2-
carrying plasma expander as a red cell substitute.