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SUMMARY:The power of chemoselectivity: Functional protein-conjugates for p
 roteomic and pharmaceutical research
DTSTART:20170119T110000
DTEND:20170119T123000
DTSTAMP:20260502T091456Z
UID:3651877e455911682b23f1ebe346e1a8c1cf7052921e39f95267ed2a
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Christian Hackenberger\, Humboldt Universität zu Berlin
  and Leibniz-Institut für Molekulare Pharmakologie (FMP) -  Berlin\nOur 
 lab constantly aims to identify new bioorthogonal reactions for the synthe
 sis and modification of functional peptides and proteins. We apply these h
 ighly selective organic reactions to study functional consequences of natu
 rally occurring posttranslational protein modifications (PTMs) as well as 
 to generate novel peptide- and protein-conjugates for pharmaceutical and m
 edicinal applications.1\nIn the first part of this lecture\, our recent ef
 forts in the synthesis and analysis of naturally occurring labile PTMs inc
 luding the synthesis of site-specifically phosphorylated Lys-peptides (pLy
 s) using the Staudinger-phosphite reaction2a as well as phosphorylated Cys
 -peptides (pCys)\,2b will be presented.\nIn the second part of this presen
 tation\, I will focus on the cellular delivery of modified functional prot
 eins. Thereby\, we employ cyclic cell penetrating peptides (cCPPs) to tran
 sport a functional full length protein to the cytosol of living cells as r
 ecently demonstrated by the direct delivery of GFP-conjugates.3 For protei
 n modification we use a combined approach of intein expression\, bioorthog
 onal reactions and recently developed enzymatic ligations\, called Tub-tag
  labeling.4 This concept is finally applied to generate site-specifically 
 labelled cell permeable nanobodies\, i.e. small antigen binding proteins t
 hat remain active within the reductive milieu inside living cells\, to int
 erfere with intracellular targets.5\nReferences\n1.  D. Schumacher\, C.P.
 R. Hackenberger\, Curr. Opin. Chem. Biol. 2014\, 22\, 62-69.\n2.  a) J. B
 ertran-Vicente\, R.A. Serwa\, M. Schümann\, P. Schmieder\, E. Krause\, C.
 P.R. Hackenberger\, J. Am Chem. Soc. 2014\, 136(39)\, 13622-13628\; b) J. 
 Bertran-Vicente\, M. Penkert\, O. Nieto\,  M. Schümann\, P. Schmieder\, 
 E. Krause\, C.P.R. Hackenberger\, Nature Comm. 2016\, 7\,12703.\n3.  N. N
 ischan\, H.D. Herce\, F. Natale\, N. Bohlke\, N. Budisa\, M.C. Cardoso\, C
 .P.R. Hackenberger\, Angew. Chem. Int. Ed. 2015\, 54(6)\, 1950-1953.\n4. 
  D. Schumacher\, J. Helma\, F.A. Mann\, G. Pichler\, F. Natale\, E. Krause
 \, M.C. Cardoso\, C.P.R. Hackenberger\, H. Leonhardt\, Angew. Chem. Int. E
 d. 2015\, 54(46)\, 13787-13791.\n5 H. Herce\, D. Schumacher\, F.A. Mann\, 
 A. Ludwig\, A. Schneider\, M. Filies\, S. Reinke\, C. Cardoso\, C.P.R. Hac
 kenberger\, submitted.\n 
LOCATION:CH G1 495 https://plan.epfl.ch/?room==CH%20G1%20495
STATUS:CONFIRMED
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