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URL:https://murmitoyen.com/events/vanille/udem/detail/778125-organic-chemis
 try-applied-to-proteins
LOCATION:Pavillon Roger-Gaudry \, 2900\, boul. Édouard-Montpetit\, Local M
 -415\, Montréal\, QC\, Canada
SUMMARY:Organic Chemistry Applied to Proteins
DESCRIPTION:Titre : Organic Chemistry Applied to Proteins: The Case of Ubiq
 uitination and Deubiquitination
\nCette conférence sera prononcée (en a
 nglais) par le Professeur Ashraf Brik de la Faculté de chimie de la Tec
 hnion-Israel Institute of Technology.
\nRésumé: In this talk\, I will pr
 esent our synthetic approaches for protein ubiquitination to shed light on
  the various unknown aspects of the ubiquitin signal in cellular pathways.
  The enzymatic attachment of ubiquitin to a specific protein target is a w
 idely utilized posttranslational modification in cellular functions and ha
 s been implicated in several diseases. The majority of biochemical\, bioph
 ysical and structural studies in the field rely on the in vitro enzymatic 
 reconstitution of this complex modification for the protein of interest. H
 owever\, the enzymatic approaches are often challenged by difficulties in 
 obtaining the ubiquitinated conjugates in acceptable homogeneity and worka
 ble quantities. Our group has been developing novel chemical approaches fo
 r the efficient and site-specific protein ubiquitination to overcome these
  limitations. Our methods combine state of the art peptide ligation approa
 ches and the use of Pd(II) complexes for the assembly of these challenging
  proteins starting from commercially available amino acids. These approach
 es allowed for the preparation of ubiquitinated protein such as alpha-synu
 clein and histone H2B to support the ongoing efforts aiming at studying th
 e effect of ubiquitination in these systems. We are also expanding these a
 pproaches to study and target important deubiquitinases\, which reverse th
 e ubiquitination step\, to shed light on their role in health and disease 
 and ultimately for drug development.
\n
\nSumeet Singh\, Indrajit Sahu\, S
 achitanand Mali\, Hosahalli Hemantha\, Oded Kleifeld\, Michael H Glickman 
 and Ashraf Brik\; Synthetic uncleavable ubiquitinated proteins dissect pro
 teasome deubiquitination and degradation\, and highlight distinctive fate 
 of tetraubiquitin\, Journal of American Chemical Society\, 2016\, 138\,160
 04.
\nMuhammad Jbara\, Suman Kumar Maity\, Mallikanti Seenaiah and Ashraf
  Brik\, Palladium Mediated Rapid Deprotection of N-terminal Cysteine Unde
 r Native Chemical Ligation Conditions for the Efficient Preparation of Syn
 thetically Challenging Proteins\, Journal of American Chemical Society\,
  2016\, 138\, 5069.
\nMichael Morgan\, Mahmood Haj-Yahya\, Alison E. Rin
 gel\, Prasanthi Bandi\, Ashraf Brik and Cynthia Wolberger\, Structural Bas
 is for Histone H2B deubiquitination by SAGA DUB Module\, Science\, 2016\, 
 351\,725.
\nMuhammad Jbara\, Suman Kumar Maity\, Michael Morgan\, Cynthia 
 Wolberger and Ashraf Brik: Total Chemical Synthesis of Phosphorylated Hist
 one H2A at Tyr57 Reveals Insight into the Inhibition Mode of the SAGA Deub
 iquitinating Module\, Angewandte Chemie Int. Ed. 2016\, 55\, 4972.
\nSomas
 ekhar Bondalapati\, Emad Eid\, Sachitanand M. Mali\, Cynthia Wolberger\, 
 Ashraf Brik\, Total Chemical Synthesis of SUMO-2-Lys63-linked Diubiquiti
 n Hybrid Chains Assisted by Removable Solubilizing Tags\, Chemical Scienc
 e\, 2017\, 8\, 4027-4034.
\n
\nInformation supplémentaireAnnonce PDF de 
 la conférence
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