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

Authors :
Thi Nguyen NT
Yun S
Lim DW
Lee EK
Source :
Preparative biochemistry & biotechnology [Prep Biochem Biotechnol] 2018; Vol. 48 (6), pp. 522-527. Date of Electronic Publication: 2018 Jun 22.
Publication Year :
2018

Abstract

'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 <superscript>®</superscript> 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.

Details

Language :
English
ISSN :
1532-2297
Volume :
48
Issue :
6
Database :
MEDLINE
Journal :
Preparative biochemistry & biotechnology
Publication Type :
Academic Journal
Accession number :
29932808
Full Text :
https://doi.org/10.1080/10826068.2018.1466157