Shielding effect of a PEG molecule of a mono-PEGylated peptide varies with PEG chain length

'Shielding' effect of a conjugated PEG molecule could cause a change in the electrostatic interaction characteristics of a PEGylate. We investigated how PEG chain length (or molecular weight) alters the electrostatic interaction potential of exenatide variants using their mono-PEGylates in...

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Bibliographic Details
Published in:Preparative biochemistry & biotechnology 2018-01, Vol.48 (6), p.522-527
Main Authors: Thi Nguyen, Ngoc-Thanh, Yun, Soi, Lim, Dong Woo, Lee, E. K.
Format: Article
Language:English
Subjects:
Amino acids
Amino Acids - analysis
Cation exchange
Cation exchange chromatography
Cation Exchange Resins
Cation exchanging
Chains
Chromatography, Ion Exchange - methods
Conjugation
Electrostatic properties
Electrostatic shielding
Elution
Exenatide - chemistry
Hydrodynamics
Hydrogen-Ion Concentration
Ions
Molecular chains
Molecular Structure
Molecular Weight
mono-PEGylate
PEG chain length
PEG hydrodynamic radius
PEGylation
Polyethylene Glycols - chemistry
Protein structure
Protein Structure, Secondary
Secondary structure
shielding effect
Sodium Chloride - chemistry
Static Electricity
Surface charge
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Summary:'Shielding' effect of a conjugated PEG molecule could cause a change in the electrostatic interaction characteristics of a PEGylate. We investigated how PEG chain length (or molecular weight) alters the electrostatic interaction potential of exenatide variants using their mono-PEGylates in a branched and linear form as model PEGylates. First, we performed the experiments to demonstrate the elution time changes of the mono-PEGylates conjugated with various MW PEGs (5, 10, 20, and 40 kD) using cation exchange chromatography (HiTrap ® SP) at various pHs (2.5, 3.0, 3.5, and 4.0). Then, we calculated the net surface charge of each mono-PEGylate to propose the PEG molecule's shielding range in terms of the number of amino acids adjacent to the conjugation residue, assuming that a PEG molecule in solution sweeps out a spherical space and an exenatide molecule have a secondary structure. The net charge calculation result was well-correlated with the experimental elution time data, where 5, 10, 20, and 40 kD PEG hindered the electrostatic potential of 5, 8, 12, and 17 amino acid residues in maximum, respectively, on each side of the conjugation point.
ISSN:1082-6068
1532-2297
DOI:10.1080/10826068.2018.1466157