Department of Chemistry
Seminar
Speaker:
<
span>Professor Dr. Christian P. R. Hackenberger
Hum
boldt Universitä\;t zu Berlin
and
Leibniz-Institut fü\
;r Molekulare Pharmakologie (FMP)
Title:
Place: Lilla hö\;rsalen\, KB3A9
Host: Chr
istian Hedberg\, Department of Chemistry
Abstr
act:
Our lab constantly aims to identify new bioorthogonal
reactions for the synthesis and modification of functional peptides and p
roteins. We apply these highly selective organic reactions to study functi
onal consequences of naturally occurring posttranslational protein modific
ations (PTMs) as well as to generate novel peptide- and protein-conjugates
for pharmaceutical and medicinal applications.(1)
In the first pa rt of this lecture\, our recent efforts in the synthesis and analysis of n aturally occurring labile PTMs including the synthesis of site-specificall y phosphorylated Lys-peptides (pLys) using the Staudinger-phosphite reacti on (2a) as well as phosphorylated Cys-peptides (pCys)\, (2b) will be prese nted.
\nIn the second part of this presentation\, I will focus on th
e cellular delivery of modified functional proteins. Thereby\, we employ c
yclic cell penetrating peptides (cCPPs) to transport a functional full len
gth protein to the cytosol of living cells as recently demonstrated by the
direct delivery of GFP-conjugates.(3) For protein modification we use a c
ombined approach of intein expression\, bioorthogonal reactions and recent
ly developed enzymatic ligations\, called Tub-tag labeling.4 This concept
is finally applied to generate site-specifically labelled cell permeable n
anobodies\, i.e. small antigen binding proteins that remain active within
the reductive milieu inside living cells\, to interfere with intracellular
targets.
References
(1.) D. Schumache
r\, C.P.R. Hackenberger\, Curr. Opin. Chem. Biol. 2014\, 22\, 62-69.
(2.) a)J. Bertran-Vicente\, R.A. Serwa\, M. Schü\;mann\, P. Sc
hmieder\, E. Krause\, C.P.R. Hackenberger\, J. Am Chem. Soc. 2014\, 136\,
13622-13628\;
(b) J. Bertran-Vicente\, M. Penkert\, O. Nieto\, M. Schü\;mann\, P. Schmieder\, E. Krause\, C.P.R. Hackenberger\, submitte d.
\n(3.) N. Nischan\, H.D. Herce\, F. Natale\, N. Bohlke\, N. Budis a\, M.C. Cardoso\, C.P.R. Hackenberger\, Angew. Chem. Int. Ed. 2015\, 54\, 1950-1953.
\n(4.) D. Schumacher\, J. Helma\, F.A. Mann\, G. Pichler \, F. Natale\, E. Krause\, M.C. Cardoso\, C.P.R. Hackenberger\, H. Leonhar dt\, Angew. Chem. Int. Ed. 2015\, 54\, 13787-13791.
DTSTART;TZID=Europe/Stockholm:20160218T150000 DTEND;TZID=Europe/Stockholm:20160218T160000 SUMMARY:Seminar - Christian P.R. Hackenberger: New chemoselective reactions for the site-specific posttranslational modification and cellular deliver y of functional proteins URL:http://www.ucmr.umu.se/about-ucmr/events/162-ucmr-calendar/164-seminar/ 408-seminar-christian-p-r-hackenberger-new-chemoselective-reactions-for-th e-site-specific-posttranslational-modification-and-cellular-delivery-of-fu nctional-proteins.html X-ALT-DESC;FMTTYPE=TEXT/HTML:Department of Chemistry
Seminar
Speaker:
Professor Dr. Christian P. R. Hackenberger
Humboldt Universitä\;t zu Berlin
and
Leibniz
-Institut fü\;r Molekulare Pharmakologie (FMP)
Ti
tle:
New chemoselective reactions for the site-specifi
c posttranslational modification and cellular delivery of functional prote
ins
Place: Lilla hö\;rsalen\, KB3A9
Host: Christian Hedberg\, Department of Chemistry
Abstract:
Our lab constantly aims to identify
new bioorthogonal reactions for the synthesis and modification of function
al peptides and proteins. We apply these highly selective organic reaction
s to study functional consequences of naturally occurring posttranslationa
l protein modifications (PTMs) as well as to generate novel peptide- and p
rotein-conjugates for pharmaceutical and medicinal applications.(1)
In the second part of this presentation\, I
will focus on the cellular delivery of modified functional proteins. Ther
eby\, we employ cyclic cell penetrating peptides (cCPPs) to transport a fu
nctional full length protein to the cytosol of living cells as recently de
monstrated by the direct delivery of GFP-conjugates.(3) For protein modifi
cation we use a combined approach of intein expression\, bioorthogonal rea
ctions and recently developed enzymatic ligations\, called Tub-tag labelin
g.4 This concept is finally applied to generate site-specifically labelled
cell permeable nanobodies\, i.e. small antigen binding proteins that rema
in active within the reductive milieu inside living cells\, to interfere w
ith intracellular targets.
References
(1.) D. Schumacher\, C.P.R. Hackenberger\, Curr. Opin. Chem. Biol. 2014\,
22\, 62-69.
(2.) a)J. Bertran-Vicente\, R.A. Serwa\, M. Sch&u
uml\;mann\, P. Schmieder\, E. Krause\, C.P.R. Hackenberger\, J. Am Chem. S
oc. 2014\, 136\, 13622-13628\;
(b) J. Bertran-Vicente\, M. Penkert \, O. Nieto\, M. Schü\;mann\, P. Schmieder\, E. Krause\, C.P.R. Hacken berger\, submitted.
\n(3.) N. Nischan\, H.D. Herce\, F. Natale\, N. Bohlke\, N. Budisa\, M.C. Cardoso\, C.P.R. Hackenberger\, Angew. Chem. Int . Ed. 2015\, 54\, 1950-1953.
\n(4.) D. Schumacher\, J. Helma\, F.A. Mann\, G. Pichler\, F. Natale\, E. Krause\, M.C. Cardoso\, C.P.R. Hackenbe rger\, H. Leonhardt\, Angew. Chem. Int. Ed. 2015\, 54\, 13787-13791.
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