PMID: 11921396Mar 29, 2002Paper

Low micromolar inhibitors of galectin-3 based on 3'-derivatization of N-acetyllactosamine

Chembiochem : a European Journal of Chemical Biology
Pernilla SörmeUlf J Nilsson

Abstract

A strategy for generating potential galectin inhibitors was devised based on derivatization at the C-3' atom in 3'-amino-N-acetyllactosamine by using structural knowledge of the galectin carbohydrate recognition site. A collection of 12 compounds was prepared by N-acylations or N-sulfonylations. Hydrophobic tagging of the O-3 atom in the N-acetylglucosamine residue with a stearic ester allowed rapid and simple product purification. The compounds were screened in a galectin-3 binding assay and three compounds with significantly higher inhibitory activities compared to the parent N-acetyllactosaminide were found. These three best inhibitors all carried an aromatic amide at the C-3' position of the galactose moiety, which indicates that favorable interactions were formed between the aromatic group and galectin-3. The best inhibitor had an IC50 value (4.4 microM) about 50 times better than the parent N-acetyllactosaminide, which implies that it has potential as a valuable tool for studying galectin-3 biological functions and also as a lead compound for the development of galectin-3-blocking pharmaceuticals.

References

May 28, 1998·The Journal of Biological Chemistry·J SeetharamanJ M Rini
Jun 13, 1998·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·N L PerilloL G Baum
Oct 6, 1999·Current Opinion in Structural Biology·J M Rini, Y D Lobsanov
Oct 16, 1999·Glycobiology·D N Cooper, S H Barondes
Dec 2, 1999·Biochimica Et Biophysica Acta·R C Hughes
Mar 7, 2000·The American Journal of Pathology·P Nangia-MakkerA Raz
Jun 14, 2000·The Journal of Biological Chemistry·J L DunphyE N Meeusen
Jun 27, 2000·International Archives of Allergy and Immunology·M Hirashima
Aug 15, 2000·Journal of Chromatography. a·U J Nilsson
Oct 12, 2000·Clinical Immunology : the Official Journal of the Clinical Immunology Society·F T Liu
Feb 24, 2001·Results and Problems in Cell Differentiation·H Leffler
Feb 24, 2001·Cancer Metastasis Reviews·P Nangia-MakkerA Raz
Apr 3, 2001·The Journal of Biological Chemistry·R Y YangF T Liu
Jan 26, 1996·The Journal of Organic Chemistry·John S. Debenham, Bert Fraser-Reid

❮ Previous
Next ❯

Citations

May 31, 2006·Cancer Immunology, Immunotherapy : CII·Mariano F Zacarías FluckO Graciela Scharovsky
Jun 16, 2007·Cancer Immunology, Immunotherapy : CII·Diego O CrociO Graciela Scharovsky
Jan 5, 2005·Nature Reviews. Cancer·Fu-Tong Liu, Gabriel A Rabinovich
May 31, 2006·Chemical Communications : Chem Comm·Denis GiguèreRené Roy
Oct 2, 2007·Journal of the American Chemical Society·M Jack Borrok, Laura L Kiessling
Nov 9, 2011·Antimicrobial Agents and Chemotherapy·Christian St-PierreMichel J Tremblay
Jun 10, 2009·Carbohydrate Research·Christopher T ObergUlf J Nilsson
Aug 5, 2008·Bioorganic & Medicinal Chemistry·Denis GiguèreRené Roy
Jun 10, 2008·Bioorganic & Medicinal Chemistry Letters·Christopher T ObergUlf J Nilsson
May 13, 2008·Carbohydrate Research·Anders BerghNina Kann
Jan 29, 2005·Chembiochem : a European Journal of Chemical Biology·Susanne M C JohanssonJan Kihlberg
Jun 6, 2009·Chembiochem : a European Journal of Chemical Biology·Monique van ScherpenzeelRoland J Pieters
Jul 17, 2007·Chembiochem : a European Journal of Chemical Biology·Ian CumpsteyUlf J Nilsson
Apr 17, 2008·Protein Science : a Publication of the Protein Society·Tiandi ZhuangJames H Prestegard
Mar 28, 2006·Chembiochem : a European Journal of Chemical Biology·Roland J Pieters
Oct 7, 2004·Analytical Biochemistry·Pernilla SörmeHakon Leffler
Feb 16, 2006·Biochimica Et Biophysica Acta·Jerka DumicMirna Flögel
Apr 20, 2005·Bioorganic & Medicinal Chemistry Letters·Johan TejlerUlf J Nilsson
Aug 12, 2014·Expert Opinion on Therapeutic Patents·Helen BlanchardKhuchtumur Bum-Erdene
Jun 29, 2014·Bioorganic & Medicinal Chemistry Letters·Vishal Kumar RajputBalaram Mukhopadhyay
Jun 12, 2010·Bioorganic & Medicinal Chemistry·Bader A SalamehUlf J Nilsson
Mar 7, 2012·Carbohydrate Research·Samy CecioniSébastien Vidal
Jun 23, 2016·International Journal of Biological Macromolecules·Tao ZhangGuihua Tai
Jun 30, 2016·Chembiochem : a European Journal of Chemical Biology·Tamara DelaineUlf J Nilsson
Nov 15, 2016·Acta Crystallographica. Section D, Structural Biology·Francesco ManzoniDerek T Logan
Feb 1, 2018·International Journal of Molecular Sciences·Yi-Chen ChanChun-Hung Lin
Oct 13, 2017·Chembiochem : a European Journal of Chemical Biology·Johann DionCyrille Grandjean
May 16, 2017·Chembiochem : a European Journal of Chemical Biology·Nadja Bertleff-ZieschangJürgen Seibel
Dec 4, 2004·Chembiochem : a European Journal of Chemical Biology·Lluis BallellRoland J Pieters
Nov 15, 2006·Organic & Biomolecular Chemistry·Lluis BallellRoland J Pieters
Apr 29, 2005·Organic & Biomolecular Chemistry·Moira AmbrosiBenjamin G Davis
Mar 24, 2005·British Journal of Cancer·G A Rabinovich

❮ 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.