title: Packing density of the PEG-shell in PEG-albumins: PEGylation induced viscosity and COP are inverse correlate of packing density.
abstract: PEG-Alb represents a new class of low viscogenic plasma expanders that achieve super perfusion in vivo by mimicking the vasodilatory influence of high viscogenic plasma expanders. PEGylation-engineered structure of PEG albumin can be envisaged as a deformable molecular domain around the rigid central protein core. The correlation between the structure of PEG-shell in terms of packing of the PEG inside the PEG shell and PEGylation induced plasma expander (PE)-like properties of albumin has been investigated as a function of the number and length of the PEG-chain. The increase in molecular radius of albumin on PEGylation is non-linear as a function of the number of PEG chains conjugated. The packing density of PEG within the PEG-shell is an inverse correlate of PEG-chain size; i.e. the shorter chains pack more compactly than the longer ones. The PEGylation induced increase in the viscosity and COP of albumin is an exponential correlation of the number of ethylene oxide units (-CH(2)-CH(2)-O-) conjugated and is also a function of the PEG-chain length. At equivalence of PEG mass conjugated, the viscosity and COP of PEG-albumin adducts correlate inversely with packing density of PEG. All PEGylated albumins are not equivalent on the basis of total PEG mass conjugated. Accordingly, the structure of PEG albumin and its solution properties can be engineered to optimize a given total PEG mass for the application of PEG albumin as a resuscitation fluid. The extension arms minimize the influence of PEG shell on the structure of the protein core. We speculate that EAF-PEGylation is a preferable platform for PEGylation of protein therapeutics and is expected to generate products with better therapeutic efficacy.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ananda
authors.forename: Belur N
authors.initials: BN
authors.lastname: Manjula
authors.forename: Fantao
authors.initials: F
authors.lastname: Meng
authors.forename: Vivek N
authors.initials: VN
authors.lastname: Acharya
authors.forename: Marcos
authors.initials: M
authors.lastname: Intaglietta
authors.forename: Seetharama A
authors.initials: SA
authors.lastname: Acharya
mesh_terms: D003102:Colloids; D006801:Humans; D008970:Molecular Weight; D009997:Osmotic Pressure; D010952:Plasma Substitutes / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011487:Protein Conformation; D055550:Protein Stability; D012709:Serum Albumin / Q000737:chemistry*; D012996:Solutions; D013696:Temperature; D014783:Viscosity
chemical_list: D003102:Colloids; D010952:Plasma Substitutes; D012709:Serum Albumin; D012996:Solutions; D011092:Polyethylene Glycols