کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1179038 | 962750 | 2008 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Non-conservative surface decoration of hemoglobin: Influence of neutralization of positive charges at PEGylation sites on molecular and functional properties of PEGylated hemoglobin Non-conservative surface decoration of hemoglobin: Influence of neutralization of positive charges at PEGylation sites on molecular and functional properties of PEGylated hemoglobin](/preview/png/1179038.png)
High hydrodynamic volume, high viscosity and high colloidal osmotic pressure (COP) of PEGylated hemoglobin (Hb) have been suggested to neutralize the vasoactivity of acellular Hb. Consequences of non-conservative PEGylation (positive charge of the amino groups at the PEGylation sites is neutralized) using succinimidyl-ester of propionic acid PEG5K on the properties of PEGylated Hb have now been investigated. Non-conservative PEGylation of Hb leads to a much higher increase in the COP and viscosity of Hb than conservative extension arm facilitated (EAF) PEGylation of Hb. Introduction of αα-fumaryl crosslinking decreased the COP of non-conservative PEGylated Hb by stabilization of interdimeric interactions. Compared to the EAF-PEGylated αα-fumaryl Hb, non-conservative PEGylated product shows a comparable COP and higher viscosity. Conservative PEGylation of αα-fumaryl Hb by reductive alkylation chemistry does not increase the COP to this level, but enhanced the molecular volume and viscosity comparable to EAF-PEGylated product. Thus, the molecular properties of PEGylated Hb can be fine tuned using different PEGylation platforms and provide a unique opportunity for the design of second generation PEGylated Hbs.
Journal: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics - Volume 1784, Issue 10, October 2008, Pages 1395–1401