Elucidation of direct competition and allosteric modulation of small-molecular-weight protein ligands using surface plasmon resonance methods

Journal of Molecular Recognition : JMR
Walter HuberSylwia Huber

Abstract

The present work introduces a surface plasmon resonance-based method for the discrimination of direct competition and allosteric effects that occur in ternary systems comprising a receptor protein and two small-molecular-weight ligands that bind to it. Fatty acid binding protein 4, fructose-1,6-bisphosphatase and human serum albumin were used as model receptor molecules to demonstrate the performance of the method. For each of the receptor molecules, pairs of ligand molecules were selected for which either direct competition or an allosteric effect had already been determined by other methods. The method of discrimination introduced here is based on the surface plasmon resonance responses observed at equilibrium when an immobilized receptor protein is brought into contact with binary mixtures of interacting ligands. These experimentally determined responses are compared with the responses calculated using a theoretical model that considers both direct competition and allosteric ligand interaction modes. This study demonstrates that the allosteric ternary complex model, which enables calculation of the fractional occupancy of the protein by each ligand in such ternary systems, is well suited for the theoretical calculation of th...Continue Reading

References

Oct 1, 1990·Journal of Molecular Recognition : JMR·L G FägerstamH Butt
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·Y XueW N Lipscomb
Apr 12, 2001·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·M AltermanA Hallberg
Aug 14, 2001·Journal of Molecular Recognition : JMR·E MandineD Lesuisse
Jul 23, 2002·Journal of Immunological Methods·Gilles ClementJacques Grassi
Oct 24, 2002·Biochemical Pharmacology·Nicole A KratochwilPaul R Gerber
Oct 27, 2004·Nature Biotechnology·Jianzhong Chen, David S Hage
May 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Mark D ErionWilliam N Lipscomb
Sep 20, 2005·Journal of Molecular Biology·Jamie GhumanStephen Curry
Nov 15, 2006·Current Pharmaceutical Design·Walter Huber, Francis Mueller
Feb 9, 2008·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Sara LejonPeter Nordberg
May 1, 2008·Drug Metabolism and Pharmacokinetics·Yukihiro KurodaTakashi Yamaoka
Jul 25, 2008·Bioorganic & Medicinal Chemistry Letters·Paul HebeisenArmin Ruf
May 1, 2009·Journal of Biomolecular Screening·Samantha PerspicaceWalter Huber
Jun 28, 2011·Nature Reviews. Drug Discovery·David C Swinney, Jason Anthony
Nov 10, 2011·Journal of Biomolecular Screening·Iva NavratilovaAndrew Cook
Aug 27, 2013·Bioorganic & Medicinal Chemistry Letters·Ulrich GrädlerTimo Heinrich
Sep 13, 2013·Medicinal Chemistry·Mingming ZhangYingxia Li
Dec 20, 2013·International Journal of Obesity : Journal of the International Association for the Study of Obesity·I SchlottmannV Lamounier-Zepter

❮ Previous
Next ❯

Citations

Jul 1, 2017·Expert Opinion on Drug Discovery·Christine C Genick, S Kirk Wright
Feb 11, 2018·Biochemical and Biophysical Research Communications·Lars EngAnders Hanning

❮ 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.