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Unité de Formation et de Recherche de Chimie
UFR926

" The power of chemoselectivity: functional protein-conjugates for intra- and extracellular targeting " Monday March 2nd 2020

 

Christian P. R. HACKENBERGER (hackenbe @ fmp-berlin.de)

 

(Humboldt University of Berlin) 

" The power of chemoselectivity: functional protein-conjugates for intra- and extracellular targeting "

Monday March 2nd 

Auditorium Astier, 11h  

 

Abstract:

Our lab aims to identify new bioorthogonal reactions for the synthesis and modification of functional peptides and proteins. We apply these highly selective organic reactions1 to study functional consequences of naturally occurring posttranslational protein modifications (PTMs), in particular phosphorylated Lys- and Cystein-peptides,2 as well as to generate novel peptide- and protein-conjugates for pharmaceutical and medicinal applications. In this presentation l will focus on the chemical modification of functional proteins as well as their cellular delivery. Thereby, we employ cyclic cell penetrating peptides (cCPPs) to transport a functional full length protein to specific intracellular compartments of living cells as recently demonstrated by the direct delivery of different fluorescent proteins.3 For protein modification we use a combined approach of intein expression as well as recently developed chemoselective reactionsand enzymatic ligations, for instance the so-called P54 or Tub-tag labeling.5  This concept is finally applied to generate new antibody-drug conjugates4b as well as cell-permeable nanobodies, i.e. small antigen binding proteins that remain active within the reductive milieu inside living cells, to interfere with intracellular targets.6 

1) Curr. Opin. Chem. Biol. 2014, 22, 62. 2)a) J. Am Chem. Soc.2014, 136, 13622; b) Nature Comm.2016, 7,12703. 3)a) Angew. Chem. Int. Ed. 2015, 54, 1950; b) Bioconjugate Chem. 2019,30,400.4)a) Angew. Chem. Int. Ed. 2019, 58, 11625; b) Angew. Chem. Int. Ed. 2019, 58, 11631; c) ChemSci. 2019, 10, 6322.5)a) Angew. Chem. Int. Ed.2015, 54, 13787, b) Chem. Sci.2017,8, 3471. 6)Nature Chem. 2017,9, 762.

04/03/20

Traductions :

    2019

    Conférenciers invités