Intrinsic thermodynamics of inhibitor binding to human carbonic anhydrase IX

Biochimica Et Biophysica Acta
Vaida LinkuvienėDaumantas Matulis

Abstract

Human carbonic anhydrase 9th isoform (CA IX) is an important marker of numerous cancers and is increasingly interesting as a potential anticancer drug target. Various synthetic aromatic sulfonamide-bearing compounds are being designed as potent inhibitors of CA IX. However, sulfonamide compound binding to CA IX is linked to several reactions, the deprotonation of the sulfonamide amino group and the protonation of the CA active site Zn(II)-bound hydroxide. These linked reactions significantly affect the affinities and other thermodynamic parameters such as enthalpies and entropies of binding. The observed and intrinsic affinities of compound binding to CA IX were determined by the fluorescent thermal shift assay. The enthalpies and entropies of binding were determined by the isothermal titration calorimetry. The pKa of CA IX was determined to be 6.8 and the enthalpy of CA IX-Zn(II)-bound hydroxide protonation was -24 kJ/mol. These values enabled the analysis of intrinsic thermodynamics of a library of compounds binding to CA IX. The most strongly binding compounds exhibited the intrinsic affinity of 0.01 nM and the observed affinity of 2 nM. The intrinsic thermodynamic parameters of compound binding to CA IX helped to draw the c...Continue Reading

References

Apr 13, 1975·Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character·R W King, A S Burgen
Aug 11, 1982·Biochimica Et Biophysica Acta·J Slavík
Mar 10, 2001·The American Journal of Pathology·S IvanovE J Stanbridge
Oct 26, 2001·Biochemical and Biophysical Research Communications·T WingoD N Silverman
Dec 25, 2002·Medicinal Research Reviews·Claudiu T SupuranAngela Casini
Aug 24, 2004·Current Medicinal Chemistry. Cardiovascular and Hematological Agents·Claudiu T. SupuranAndrea Scozzafava
Apr 20, 2006·Archives of Biochemistry and Biophysics·Jukka KervinenIngrid Deckman
Apr 7, 2007·Cancer Metastasis Reviews·Pawel SwietachAdrian L Harris
Apr 18, 2007·Journal of Biomolecular Screening·Tara M MezzasalmaMatthew J Todd
Apr 19, 2007·Chemistry, an Asian Journal·Vijay M KrishnamurthyGeorge M Whitesides
May 4, 2007·Bioorganic & Medicinal Chemistry·Claudiu T Supuran, Andrea Scozzafava
Oct 20, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bradley C LeibovichEugene D Kwon
Jan 3, 2008·Nature Reviews. Drug Discovery·Claudiu T Supuran
Aug 16, 2008·The Journal of Biological Chemistry·Mika HilvoSeppo Parkkila
Dec 5, 2009·Nature Reviews. Drug Discovery·John E LadburyErnesto Freire
Feb 20, 2010·Journal of Enzyme Inhibition and Medicinal Chemistry·Lina BaranauskienėDaumantas Matulis
Oct 12, 2010·Bioorganic & Medicinal Chemistry·Edita ČapkauskaitėDaumantas Matulis
Oct 15, 2010·Biophysical Chemistry·Asta ZubrienėDaumantas Matulis
Jun 2, 2012·PloS One·Egidijus KazlauskasDaumantas Matulis
Jun 9, 2012·BMC Biophysics·Lina Baranauskienė, Daumantas Matulis
Nov 20, 2012·Bioorganic & Medicinal Chemistry·Vaida JogaitėDaumantas Matulis
Nov 22, 2012·Bioorganic & Medicinal Chemistry·Tiphaine Rogez-FlorentLaurence Goossens
Jan 30, 2013·Journal of Enzyme Inhibition and Medicinal Chemistry·Asta ZubrienėDaumantas Matulis
Mar 16, 2013·Journal of Enzyme Inhibition and Medicinal Chemistry·Aditi SharmaClaudiu T Supuran
Apr 25, 2014·Journal of Enzyme Inhibition and Medicinal Chemistry·Vaida MorkūnaitėDaumantas Matulis
Jun 27, 2014·BioMed Research International·Dovile DekaminaviciuteAurelija Zvirbliene
Aug 15, 2014·Seminars in Cancer Biology·Jaromir Pastorek, Silvia Pastorekova
Oct 31, 2014·Journal of Medicinal Chemistry·Virginija DudutienėDaumantas Matulis
Jan 24, 2015·Nature Reviews. Drug Discovery·Gerhard Klebe
Feb 6, 2015·Journal of Molecular Recognition : JMR·Vilma Pilipuitytė, Daumantas Matulis

❮ Previous
Next ❯

Citations

Oct 25, 2016·Journal of Biotechnology·Vaida JuozapaitienėDaumantas Matulis
Feb 6, 2017·Analytical Biochemistry·Joana SmirnovienėDaumantas Matulis
Mar 10, 2017·Expert Opinion on Drug Discovery·Rafael Claveria-GimenoAdrian Velazquez-Campoy
Oct 5, 2017·European Biophysics Journal : EBJ·Aurelija MickevičiūtėDaumantas Matulis
Sep 5, 2019·Scientific Reports·Justina KazokaitėDaumantas Matulis
May 5, 2021·ChemistryOpen·Joana SmirnovienėDaumantas Matulis
Feb 22, 2018·Journal of Medicinal Chemistry·Vaida LinkuvienėDaumantas Matulis

❮ 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.