Investigating the Role of Artemin Glycosylation

Pharmaceutical Research
Qiu DanwenDamian Houde

Abstract

Oligosaccharides play diverse and unpredictable functional roles when attached to proteins and are a largely unexplored scaffold for deconstructing and attributing novel functions to proteins during drug development. Here, the glycoprotein Artemin (ART) was carefully assessed by multiple analytical methods that allow us to provide a comprehensive understanding of how N-linked glycosylation impact the structural and functional properties of ART. Modification of the N-linked glycan of ART was performed by incubation with various enzymes. Biological assays and systems were used to examine the relative activity and pharmacokinetic properties of ART as a function of glycosylation. In order to reveal the conformational impact of glycosylation on ART, hydrogen/deuterium exchange mass spectrometry (HDX-MS) was employed in addition to differential scanning calorimetry. The colloidal stability of ART glycovariants was assessed by dynamic light scattering, viscometry, and solubility assays. No difference in pharmacokinetics or relative potency was revealed between glycosylated and nonglycosylated ART. Surprisingly, the HDX-MS data indicated that the glycan does not greatly influence the conformation and dynamics of the protein. In contras...Continue Reading

References

Jan 1, 1973·Biopolymers·M KomatsubaraY Wada
Sep 1, 1993·Proteins·Y BaiS W Englander
Sep 1, 1993·Proteins·G P ConnellyS W Englander
Jun 10, 1997·Proceedings of the National Academy of Sciences of the United States of America·M SanicolaR L Cate
May 20, 1998·Proceedings of the National Academy of Sciences of the United States of America·R H BalohJ Milbrandt
Aug 14, 1998·The Journal of Comparative Neurology·J P GoldenE M Johnson
Oct 16, 1999·The Journal of Biological Chemistry·R Kundra, S Kornfeld
Mar 4, 2000·Journal of Pharmaceutical and Biomedical Analysis·M D SadickV Ling
Jun 26, 2001·The European Journal of Neuroscience·O E OrozcoM Sanicola
Sep 7, 2001·Cytokine & Growth Factor Reviews·M Takahashi
May 4, 2002·Nature Reviews. Neuroscience·Matti S Airaksinen, Mart Saarma
Feb 25, 2003·Annual Review of Biophysics and Biomolecular Structure·Andrew N HoofnagleNatalie G Ahn
May 30, 2003·Proceedings of the National Academy of Sciences of the United States of America·Joan J EnglanderVirgil L Woods
Apr 1, 1953·The Journal of Clinical Investigation·B PIROFSKY
Oct 7, 2003·Nature Medicine·Luis R GardellFrank Porreca
Feb 7, 2004·European Journal of Biochemistry·Harrie A van VeenJan H Nuijens
Jun 3, 2004·Chembiochem : a European Journal of Chemical Biology·Hans-Joachim GabiusHarold Rüdiger
Oct 7, 2005·Mass Spectrometry Reviews·Thomas E Wales, John R Engen
Jun 1, 2006·Biochemistry·Laura SilvianAnthony Rossomando
Aug 26, 2006·Journal of the American Society for Mass Spectrometry·David D WeisIgnatius J Kass
Oct 13, 2006·Annual Review of Immunology·James N ArnoldRaymond A Dwek
Jun 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Dalit Shental-Bechor, Yaakov Levy
Feb 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sarah R HansonEvan T Powers
Aug 26, 2009·Journal of Pharmaceutical Sciences·Sandeep YadavDevendra S Kalonia
Jan 28, 2010·Molecular & Cellular Proteomics : MCP·Damian HoudeJohn R Engen
Sep 8, 2010·Journal of Pharmaceutical Sciences·Sandeep YadavDevendra S Kalonia
Dec 22, 2010·Chemical Society Reviews·Lars KonermannYu-Hong Liu
Feb 5, 2011·Journal of Pharmaceutical Sciences·Christian LehermayrStefan Fischer

❮ Previous
Next ❯

Citations

Feb 10, 2017·Protein Engineering, Design & Selection : PEDS·Richelle SopkoBlake Pepinsky
Jul 5, 2017·The Biochemical Journal·Nisha Grandhi Jayaprakash, Avadhesha Surolia
Feb 26, 2020·Journal of Pharmaceutical and Biomedical Analysis·Natalia PennerBlake Pepinsky

❮ Previous
Next ❯

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.