CONTROLLED CuAAC PROTEIN PEGYLATION WITH AZIDE BRANCHING REAGENTS
https://doi.org/10.29235/1561-8331-2018-54-2-197-203
Abstract
Polyethyleneglycol (PEG) is nontoxic, nonimmunogenic, hydrophilic, chargeless and nonbiodegradable poliymer. Its usage as a part of therapeutics protein drugs is common in medicine practice. It is known that covalent attachment of PEG conduces to prolong blood circulation half-lives, improves drug solubility and stability and reduces immunogenicity. It allows optimizing pharmacodynamic and pharmacokinetic drug properties. The goal of structure optimization
of therapeutic proteins conjugates with PEG is to reduce loss of biological activity. It can be reached through controlled site- specific pegylation. We introduce two-step modification of proteins with branched polyethylenglycols via click-chemistry, synthesis of branched PEG azide reagent on the base of tris(hydroxymethyl)aminomethane with three linear PEG polymers. At first, we introduce alkyne groups with NHS-ester of alkyne acid in BSA protein. Then, branched PEG azide reagent reacts with alkyne function via CuAAC. Purification of the conjugates was done via gel-chromotography. Number of modifications was calculated from MALDI mass-spectra.
About the Authors
Yu. V. Martynenko-Makaev
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus .
Belarus
Belarus
Yury V. Martynenko-Makaev – Researcher.
13, Surganov Str., 220072, Minsk.
A. S. Kruhlik
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus .
Belarus
Belarus
Aliaksandr S. Kruhlik – Junior researcher.
13, Surganov Str., 220072, Minsk.
O. L. Sharko
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus .
Belarus
Belarus
Olga L. Sharko – Ph. D. (Chemistry), Senior researcher.
13, Surganov Str., 220072, Minsk.
V. V. Shmanai
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus .
Belarus
Belarus
Vadim V. Shmanai – Ph. D. (Chemistry), Head of the Laboratory.
13, Surganov Str., 220072, Minsk.
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