ASGPR-Mediated Uptake of Multivalent Glycoconjugates for Drug Delivery in Hepatocytes

Chembiochem : a European Journal of Chemical Biology
Marie MonestierPascale Delangle

Abstract

Liver cells are an essential target for drug delivery in many diseases. The hepatocytes express the asialoglycoprotein receptor (ASGPR), which promotes specific uptake by means of N-acetylgalactosamine (GalNAc) recognition. In this work, we designed two different chemical architectures to treat Wilson's disease by intracellular copper chelation. Two glycoconjugates functionalized with three or four GalNAc units each were shown to enter hepatic cells and chelate copper. Here, we studied two series of compounds derived from these glycoconjugates to find key parameters for the targeting of human hepatocytes. Efficient cellular uptake was demonstrated by flow cytometry using HepG2 human heptic cells that express the human oligomeric ASGPR. Dissociation constants in the nanomolar range showed efficient multivalent interactions with the receptor. Both architectures were therefore concluded to be able to compete with endogeneous asialoglycoproteins and serve as good vehicles for drug delivery in hepatocytes.

References

Oct 1, 1992·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Y C Lee
Jan 1, 1982·Annual Review of Biochemistry·G Ashwell, J Harford
Apr 28, 1995·Journal of Medicinal Chemistry·E A BiessenT J van Berkel
Jun 26, 2001·Glycoconjugate Journal·R T Lee, Y C Lee
Dec 26, 2001·Chemical Reviews·B Sarkar
Mar 27, 2004·Chemical Communications : Chem Comm·Olivier SénèquePascale Delangle
Oct 18, 2005·Movement Disorders : Official Journal of the Movement Disorder Society·John M Walshe
Mar 25, 2008·Bioorganic & Medicinal Chemistry·Oleg KhorevBeat Ernst
May 21, 2009·Journal of the American Chemical Society·Anaïs M PujolPascale Delangle
Sep 19, 2009·Bioorganic & Medicinal Chemistry·Daniela StokmaierBeat Ernst
Jun 15, 2010·Journal of the American Chemical Society·Sai Kumar RamaduguClaudio J Margulis
Oct 20, 2010·Best Practice & Research. Clinical Gastroenterology·Dominik Huster
Dec 16, 2010·Journal of the American Chemical Society·Anaïs M PujolPascale Delangle
Mar 19, 2011·Chemistry : a European Journal·Anaïs M PujolPascale Delangle
Feb 14, 2012·Dalton Transactions : an International Journal of Inorganic Chemistry·Pascale Delangle, Elisabeth Mintz
Jun 26, 2012·Angewandte Chemie·Anaïs M PujolPascale Delangle
Dec 25, 2012·Chemical Society Reviews·M Carmen GalanOlivier Renaudet
Jul 31, 2013·Bioconjugate Chemistry·Nathalie BerthetOlivier Renaudet
Mar 13, 2014·Annals of the New York Academy of Sciences·Christelle Gateau, Pascale Delangle
Feb 24, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Anisha A D'Souza, Padma V Devarajan
Mar 20, 2015·Chembiochem : a European Journal of Chemical Biology·Kallanthottathil G RajeevMuthiah Manoharan

❮ Previous
Next ❯

Citations

Dec 15, 2016·Bioconjugate Chemistry·Xiangang HuangBastien Castagner
Jul 7, 2017·Chemical Reviews·Carlo PifferiOlivier Renaudet
Apr 12, 2018·Physiology·Fred G Pluthero, Walter H A Kahr
Jun 13, 2017·Organic & Biomolecular Chemistry·Antoine HoangOlivier Renaudet
Nov 16, 2019·International Journal of Molecular Sciences·Laura GauthierIsabelle Texier
May 14, 2020·Metallomics : Integrated Biometal Science·Marie MonestierElisabeth Mintz
Sep 17, 2020·Journal of Drug Targeting·Laura GauthierChristelle Gateau
Dec 15, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hongzhi WangPeixuan Guo
Aug 3, 2021·Chemical Reviews·Lu SuGuosong Chen
Jul 3, 2019·ACS Central Science·Dhanusha A NalawanshaCraig M Crews
Dec 3, 2020·Molecular Pharmaceutics·Rostislav A PetrovAlexander G Majouga

❮ 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.