Modification with polysialic acid-PEG copolymer as a new method for improving the therapeutic efficacy of proteins

Preparative Biochemistry & Biotechnology
Jian Rong WuXiaobei Zhan

Abstract

A new protein derivatization method was developed with a block copolymer to reduce the immunogenicity of therapeutic proteins. The block copolymer consisted of polyethylene glycol (PEG) and polysialic acid (PSA), a nonimmunogenic and biodegradable biopolymer. Uricase was used as a model protein. Molecular weight analysis results indicated that the uricase-PEG-PSA conjugate was linked with 2.5 copolymers for each uricase unit. The residual enzyme activity of the uricase with modification by the PEG-PSA copolymer was 72.4%. The tolerance and stability to heat, acid, alkaline, and trypsin treatments significantly improved compared with the native uricase. The immunogenicity of uricase modified with PEG-PSA copolymer was remarkably reduced. The transmission electron microscopy results of the uricase-PEG-PSA conjugate showed a spherical hydrated shell with a larger particle size. These findings proved that the PSA-PEG-protein conjugate is a formulation that can potentially be used to deliver the protein and peptide-based drugs.

References

Mar 1, 1975·Analytical Biochemistry·S L Snyder, P Z Sobocinski
Jul 1, 1989·Analytical Biochemistry·R E BrownK J Hyland
Mar 7, 1996·Biochimica Et Biophysica Acta·A I Fernandes, G Gregoriadis
Jul 1, 1996·The Biochemical Journal·R M DanielH H Petach
Aug 15, 1997·Biochimica Et Biophysica Acta·A I Fernandes, G Gregoriadis
Apr 9, 2001·International Journal of Pharmaceutics·A I Fernandes, G Gregoriadis
Jun 8, 2001·Journal of Controlled Release : Official Journal of the Controlled Release Society·G M ZentnerS Weitman
Jul 19, 2001·Bioconjugate Chemistry·P CalicetiF M Veronese
Aug 21, 2001·Clinical Pharmacokinetics·J M HarrisM Modi
Apr 17, 2002·International Journal of Pharmaceutics·Alexandre Learth SoaresJosé Abrahão-Neto
Jun 28, 2003·Biochimica Et Biophysica Acta·Sanjay JainGregory Gregoriadis
Jul 1, 1961·Biochemical Pharmacology·G L ELLMANR M FEATHER-STONE
Jul 5, 2005·Expert Opinion on Investigational Drugs·M JordinsonM Pignatelli
Aug 4, 2005·Pharmaceutical Research·Jose RamonEugenio Hardy
Mar 27, 2007·Chemical Biology & Drug Design·Huaizhi DouChunhua Yin
Sep 11, 2007·Advanced Drug Delivery Reviews·Merry R ShermanFernando Perez-Ruiz
Oct 29, 2008·Pharmaceutical Research·Eric A SimoneVladimir R Muzykantov
Feb 26, 2009·Journal of Controlled Release : Official Journal of the Controlled Release Society·Arvind K JainSuresh P Vyas
Dec 9, 2009·International Journal of Pharmaceutics·Débora da Silva FreitasJosé Abrahão-Neto
Jan 6, 2010·Journal of Pharmaceutical Sciences·Dipak S PisalSathy V Balu-Iyer
Jan 5, 2011·Nature Reviews. Drug Discovery·Naomi SchlesingerPeter Kirkpatrick
Aug 31, 2012·Expert Opinion on Drug Delivery·Ricardo P GarayPascal Richette
Dec 12, 2012·The Journal of Pharmacy and Pharmacology·Hong TianWenbing Yao
Jan 9, 2013·Proceedings of the National Academy of Sciences of the United States of America·Denis G IlyushinAlexander G Gabibov
May 16, 2013·Pharmaceutical Research·Huub SchellekensVera Brinks
Jun 27, 2013·Biochimica Et Biophysica Acta·Manaswini SivaramakrishnanFriedrich Metzger
Nov 7, 2014·Critical Reviews in Biochemistry and Molecular Biology·Karen J ColleyChihiro Sato
Mar 7, 2013·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Liming ZhangNongyue He

❮ Previous
Next ❯

Methods Mentioned

BETA
light
light scattering
enzyme-linked immunosorbent assay
ELISA
Transmission electron microscopy

Software Mentioned

ASTRA

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2021 Meta ULC. All rights reserved