Induced plasma expander-like properties as a function of PEG-chains on extension arm facilitated PEGylation of albumin: "mushroom to brush-like" conformational transition of the PEG-albumin conjugate.
Plasma expander-like properties of albumin induced on hexa as well as dodecacPEGylation using Extension Arm Facilitated PEGylation platform make it an excellent resuscitation fluid. PEGylation induced changes in the structure, drug binding, and plasma expander-like properties of bovine serum albumin has been now investigated as a function of PEGylation. The molecular volume of albumin increases on PEGylation nearly linearly; in the beginning up to about six PEG chains are conjugated, then plateau off, while the viscosity and colloidal osmotic pressure change very little initially and then increase exponentially as a function of PEG chains conjugated. PEGylation has essentially no influence on the secondary structure or drug properties of albumin. Tryphtophyl fluorescence of albumin is quenched on PEGylation as a direct correlate of the changes in molecular radius of PEG-albumin. It is concluded that hexaPEGylated and dodecaPEGylated albumin belong to two different configurational states of PEG-albumin in terms of packing of PEG-chains on the molecular surface of the protein. The results suggest a transition of PEGylated albumin from the initial mushroom-like conformation to brush conformation as the PEGylation increases. The therapeutic efficacy of the two PEGylated species is needed to establish the optimum level of PEGylation to function as resuscitation fluids.
Sahu
Ranjit K
RK
Department of Medicine, Albert Einstein College of Medicine, Bronx, N Y 10461, USA.
Nacharaju
Parimala
P
Manjula
Belur N
BN
Acharya
Seetharama A
SA
D000818:Animals; D002417:Cattle; D008968:Molecular Conformation; D009997:Osmotic Pressure; D011092:Polyethylene Glycols / Q000737:chemistry*; D011487:Protein Conformation; D012151:Resuscitation / Q000379:methods; D012709:Serum Albumin / Q000737:chemistry* / Q000627:therapeutic use*; D014783:Viscosity
D012709:Serum Albumin; D011092:Polyethylene Glycols