Biomimetic deiodination of thyroid hormones and iodothyronamines - a structure-activity relationship study

Organic & Biomolecular Chemistry
Santanu Mondal, Govindasamy Mugesh

Abstract

Mammalian selenoenzymes, iodothyronine deiodinases (DIOs), catalyze the tyrosyl and phenolic ring deiodination of thyroid hormones (THs) and play an important role in maintaining the TH concentration throughout the body. These enzymes also accept the decarboxylated thyroid hormone metabolites, iodothyronamines (TAMs), as substrates for deiodination. Naphthalene-based selenium and/or sulphur-containing small molecules have been shown to mediate the regioselective tyrosyl ring deiodination of thyroid hormones and their metabolites. Herein, we report on the structure-activity relationship studies of a series of peri-substituted selenium-containing naphthalene derivatives for the deiodination of thyroid hormones and iodothyronamines. Single crystal X-ray crystallographic and (77)Se NMR spectroscopic studies indicated that the intramolecular SeX (X = N, O and S) interactions play an important role in the deiodinase activity of the synthetic mimics. Furthermore, the decarboxylated metabolites, TAMs, have been observed to undergo slower tyrosyl ring deiodination than THs by naphthyl-based selenium and/or sulphur-containing synthetic deiodinase mimics and this has been explained on the basis of the strength of SeI halogen bonding forme...Continue Reading

References

Mar 1, 1979·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·K Sorimachi, H J Cahnmann
Dec 31, 1990·Biochemical and Biophysical Research Communications·D BehneJ Köhrle
Jan 1, 1995·Annual Review of Nutrition·P R Larsen, M J Berry
Aug 1, 1997·Thyroid : Official Journal of the American Thyroid Association·D L St Germain, V A Galton
Oct 29, 1997·Journal of Molecular Endocrinology·S G BallW W Chin
Jul 20, 1999·Molecular and Cellular Endocrinology·J Köhrle
Mar 20, 2002·Methods in Enzymology·J Köhrle
May 18, 2004·Nature Medicine·T S ScanlanDavid K Grandy
Jul 15, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Antonia LanniFernando Goglia
Sep 1, 2005·Thyroid : Official Journal of the American Thyroid Association·George G J M KuiperTheo J Visser
Sep 22, 2005·Endocrine Reviews·J KöhrleJ E Dumont
Feb 3, 2006·Journal of Medicinal Chemistry·Matthew E HartT S Scanlan
Nov 8, 2006·British Journal of Pharmacology·R ZucchiDavid K Grandy
May 29, 2007·ACS Chemical Biology·Aaron N SneadT S Scanlan
Mar 15, 2008·Endocrinology·S PiehlJ Köhrle
Jul 25, 2008·Angewandte Chemie·Pierangelo MetrangoloGiancarlo Terraneo
Apr 2, 2009·Nature Reviews. Drug Discovery·John D Baxter, Paul Webb
Oct 14, 2010·Angewandte Chemie·Debasish Manna, Govindasamy Mugesh
Jun 9, 2011·Journal of the American Chemical Society·Debasish Manna, Govindasamy Mugesh
Apr 3, 2014·The Journal of Endocrinology·Alvaro Souto PadronDenise Pires de Carvalho
Apr 3, 2014·Physiological Reviews·Rashmi MullurGregory A Brent
Jul 26, 2014·Chemistry : a European Journal·Santanu Mondal, Govindasamy Mugesh
Dec 10, 2014·Chemistry : a European Journal·Debasish MannaGovindasamy Mugesh
Jul 28, 2015·Angewandte Chemie·Santanu Mondal, Govindasamy Mugesh
Sep 9, 2015·Endocrinology·Carolin S HoefigJ Köhrle
Sep 12, 2015·Angewandte Chemie·Ulrich Schweizer, Clemens Steegborn
May 27, 2016·Angewandte Chemie·Santanu MondalGovindasamy Mugesh

Citations

Apr 15, 2017·Molecular and Cellular Endocrinology·Santanu Mondal, Govindasamy Mugesh
Nov 7, 2018·Chemistry : a European Journal·Santanu Mondal, Govindasamy Mugesh
Nov 28, 2019·Chembiochem : a European Journal of Chemical Biology·Santanu MondalGovindasamy Mugesh

Related Concepts

Halogens
Iodide Peroxidase
Iodothyronine Deiodinase
Selenium
Thyroid Gland
Thyroid Hormones
Crystallography, X-Ray
Cyclo(tyrosyl-tyrosyl)
Phenolics
Selenium supplement

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.

Alzheimer's Disease: MS4A

Variants within the membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease in genome-wide association studies. Here is the latest research on Alzheimer's disease and MS4A.

Pediculosis pubis

Pediculosis pubis is a disease caused by a parasitic insect known as Pthirus pubis, which infests human pubic hair, as well as other areas with hair including eye lashes. Here is the latest research.

Rh Isoimmunization

Rh isoimmunization is a potentially preventable condition that occasionally is associated with significant perinatal morbidity or mortality. Discover the latest research on Rh Isoimmunization here.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells. It also follows CRISPR-Cas9 approaches to generating genetic mutants as a means of understanding the effect of genetics on phenotype.

Enzyme Evolution

This feed focuses on molecular models of enzyme evolution and new approaches (such as adaptive laboratory evolution) to metabolic engineering of microorganisms. Here is the latest research.

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.

Pharmacology of Proteinopathies

This feed focuses on the pharmacology of proteinopathies - diseases in which proteins abnormally aggregate (i.e. Alzheimer’s, Parkinson’s, etc.). Discover the latest research in this field with this feed.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.

Related Papers

Nihon rinsho. Japanese journal of clinical medicine
N ToyodaMitsushige Nishikawa
Trends in Endocrinology and Metabolism : TEM
D L St Germain
© 2021 Meta ULC. All rights reserved