Alpha Synuclein Fibrils Contain Multiple Binding Sites for Small Molecules

ACS Chemical Neuroscience
Chia-Ju HsiehRobert H Mach

Abstract

The fibrillary aggregation of the protein alpha synuclein (Asyn) is a hallmark of Parkinson's disease, and the identification of small molecule binding sites on fibrils is essential to the development of diagnostic imaging probes. A series of molecular modeling, photoaffinity labeling, mass spectrometry, and radioligand binding studies were conducted on Asyn fibrils. The results of these studies revealed the presence of three different binding sites within fibrillar Asyn capable of binding small molecules with moderate to high affinity. A knowledge of the amino acid residues in these binding sites will be important in the design of high affinity probes capable of imaging fibrillary species of Asyn.

References

Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K UédaT Saitoh
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·M G SpillantiniM Goedert
Apr 21, 1999·Rapid Communications in Mass Spectrometry : RCM·M PuchadesP Davidsson
Nov 1, 2003·Science·A B SingletonK Gwinn-Hardy
Mar 3, 2004·Annals of Neurology·William E KlunkBengt Långström
Sep 29, 2004·Lancet·Marie-Christine Chartier-HarlinAlain Destée
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Apr 3, 2007·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Yukitsuka KudoHiroyuki Arai
Jun 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Marçal VilarRoland Riek
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
May 27, 2010·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Dean F WongMichael J Pontecorvo
Jul 25, 2012·Archives of Neurology·Paul T KotzbauerJoel S Perlmutter
Dec 14, 2012·Journal of Alzheimer's Disease : JAD·David T ChienHartmuth C Kolb
Dec 24, 2015·Organic & Biomolecular Chemistry·Conor M HaneyE James Petersson
Mar 29, 2016·Nature Structural & Molecular Biology·Marcus D TuttleChad M Rienstra
Apr 5, 2016·Journal of Neuroscience Methods·A McCormackT Chataway
May 5, 2016·Nature Structural & Molecular Biology·Wouter Peelaerts, Veerle Baekelandt
Jan 10, 2018·Chemical Communications : Chem Comm·Conor M Haney, E James Petersson
Feb 21, 2018·Nature Communications·Janin LautenschlägerGabriele S Kaminski Schierle
Feb 28, 2018·Bioorganic & Medicinal Chemistry Letters·Xuyi YueZhude Tu

❮ Previous
Next ❯

Citations

Feb 28, 2020·Chemical Communications : Chem Comm·Zsofia Lengyel-ZhandRobert H Mach
Dec 15, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Alberto CornejoFrancisco Melo
Dec 29, 2020·European Journal of Nuclear Medicine and Molecular Imaging·Laura KueblerKristina Herfert
Feb 17, 2021·PET Clinics·Kirk A Frey, Nicolaas I L J Bohnen
Oct 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Vladimir I MuronetzMatej Sova
Sep 18, 2021·Journal of Neurochemistry·Natasha S R BidesiMatthias M Herth
Dec 16, 2021·ACS Chemical Neuroscience·Sho KaideMasahiro Ono

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.

Alpha-Synuclein Aggregation

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.

Related Papers

The Journal of Biological Chemistry
R E GalardyM P Printz
Methods in Enzymology
H Bayley, J R Knowles
Bollettino della Società italiana di biologia sperimentale
M CordaF Riva
© 2022 Meta ULC. All rights reserved