New leads for fragment-based design of rhenium/technetium radiopharmaceutical agents

IUCrJ
Alice Brink, J Helliwell

Abstract

Multiple possibilities for the coordination of fac-[Re(CO)3(H2O)3]+ to a protein have been determined and include binding to Asp, Glu, Arg and His amino-acid residues as well as to the C-terminal carboxylate in the vicinity of Leu and Pro. The large number of rhenium metal complex binding sites that have been identified on specific residues thereby allow increased target identification for the design of future radiopharmaceuticals. The core experimental concept involved the use of state-of-art tuneable synchrotron radiation at the Diamond Light Source to optimize the rhenium anomalous dispersion signal to a large value (f'' of 12.1 electrons) at its LI absorption edge with a selected X-ray wavelength of 0.9763 Å. At the Cu Kα X-ray wavelength (1.5418 Å) the f'' for rhenium is 5.9 electrons. The expected peak-height increase owing to the optimization of the Re f'' was therefore 2.1. This X-ray wavelength tuning methodology thereby showed the lower occupancy rhenium binding sites as well as the occupancies of the higher occupancy rhenium binding sites.

References

May 18, 1999·Acta Crystallographica. Section D, Biological Crystallography·E A Merritt
May 31, 2002·Acta Crystallographica. Section B, Structural Science·Frank H Allen
Mar 29, 2003·Biochemical Pharmacology·Nuno C SantosCarlota Saldanha
Jul 15, 2004·Dalton Transactions : an International Journal of Inorganic Chemistry·Stefan MundwilerRoger Alberto
Nov 24, 2004·Journal of Chemical Information and Computer Sciences·Ian J BrunoA Guy Orpen
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Dec 25, 2007·Acta Crystallographica. Section A, Foundations of Crystallography·George M Sheldrick
May 30, 2008·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Mariantonella ColucciStefano Pieretti
Nov 20, 2008·Acta Crystallographica. Section D, Biological Crystallography·Michele CianciAtsuo Suzuki
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Alexei Vagin, Alexei Teplyakov
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·T Geoff G BattyeAndrew G W Leslie
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·S McNicholasM E M Noble
Jun 23, 2011·Topics in Current Chemistry·Daniel A Erlanson
Aug 2, 2011·Metallomics : Integrated Biometal Science·Sarah L BinkleyChristopher J Ziegler
Jan 11, 2012·Inorganic Chemistry·Fabio Zobi, Bernhard Spingler
Feb 9, 2012·Metallomics : Integrated Biometal Science·Giuseppe SantoroFabio Zobi
Mar 31, 2012·Trends in Pharmacological Sciences·Christopher W MurrayDavid C Rees
Apr 17, 2012·Acta Crystallographica. Section D, Biological Crystallography·Pavel V AfoninePaul D Adams
Apr 25, 2012·Acta Crystallographica. Section D, Biological Crystallography·Simon W M TanleyJohn R Helliwell
Sep 17, 2013·Journal of the American Chemical Society·Kana TakematsuHarry B Gray
Feb 5, 2014·Journal of Chemical Information and Modeling·Diane Joseph-McCarthyDemetri Moustakas
Sep 10, 2014·Acta Crystallographica. Section D, Biological Crystallography·Andrey A Lebedev, Michail N Isupov
Sep 10, 2014·Acta Crystallographica. Section F, Structural Biology Communications·Simon W M Tanley, John R Helliwell
Nov 26, 2015·Acta Crystallographica. Section E, Crystallographic Communications·Alexander A Golichenko, Alexander V Shtemenko
Aug 17, 1998·Angewandte Chemie·Mirka BergamoAngelo Sironi

❮ Previous
Next ❯

Citations

Jun 16, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Chilaluck C KonkankitJustin J Wilson
Sep 3, 2019·Current Pharmaceutical Design·Philippe ColleryVeena Vijaykumar
Apr 21, 2018·Nature Protocols·Katarzyna B HandingWladek Minor
Jul 14, 2018·IUCrJ·Sahir KhurshidNaomi E Chayen
Jan 20, 2021·Chemical Communications : Chem Comm·Antonello Merlino
Jun 28, 2019·Chemical Reviews·Robin Taylor, Peter A Wood

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
protein crystallography

Software Mentioned

MOSFLM
SHELXL
REFMAC
Bruker PROTEUM
SHELXTL
Coot
PHENIX
CCP
Phaser

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.

Related Papers

Science Progress
Christopher J Rhodes
Nature Structural Biology
C Jacobsen, J Kirz
European Journal of Biochemistry
Kjell Håkansson, Charles G Miller
© 2022 Meta ULC. All rights reserved