CPS Meeting 2019
Please find informations on our final project report meeting here:
Conference report:
PDF-File (1,7 mB)
Conference website:
www.cps2019.de
SPP 1623 Contact
Geschäftsstelle des SPP 1623
Tel.: 030 94793 180
Fax: 030 94793 188
Robert-Rössle Str. 10, Geb. 81
13125 Berlin
Bürkle/Marx
Targeted poly(ADP-ribosyl)ation of proteins
ADP-ribosylation and poly(ADP-ribosyl)ation are reversible posttranslational modifications of proteins catalyzed by ADP-ribosyltransferases (ARTs) like poly(ADP-ribose) polymerases (PARPs) using NAD+ as substrate. Poly(ADP-ribose) (PAR) is a linear or multibranched polyanion of variable size that can interact noncovalently with numerous proteins. PAR formation has been associated with DNA repair, maintenance of genomic stability, transcription, telomere regulation, cell division, energy metabolism, cell death, tumour suppression and ageing. However, our knowledge of how PAR and ADP-ribose modifications modulate the properties and regulate the function of their target proteins is sparse.
For a better understanding of these modifications and their biological role we propose the synthesis of proteins with distinct sites of mono- and poly(ADP-ribosyl)ation. The generated functionalized proteins will be of major interest and the basis for comprehensive biochemical follow-up studies. By the incorporation of alkyne-modified unnatural amino acids via amber-stop-codon suppression, site-specific modification of proteins with orthogonally reacting functional groups is feasible. Subsequently, new ligation chemistry will be developed to offer a powerful tool to conjugate the unnatural amino acid site-specifically e.g. with azide-modified ADP-ribose and PAR. Such well-defined functionalized proteins will be used to investigate the biological role of mono- and poly(ADP-ribosyl)ation of the two exemplary histones H1 and H2.B, whose PARmodification has been revealed as a regulator of chromatin structure.
Prof. Dr. Alexander Bürkle
Universität Konstanz
Tel.: +49 7531 88 - 4035
Fax: +49 7531 88 - 4033
Prof. Dr. Andreas Marx
Universität Konstanz
Tel.: +49 7531 88 - 5139
Fax: +49 7531 88 - 5140
Publications within the SPP 1623 project
Y. Wang, D. Rösner, M. Grzywa, A. Marx
Angew. Chem. Int. Ed. 2014, 53, 8159-8162.
Chain terminating and clickable NAD+ analogues for labeling target proteins of ADP-ribosyltransferases
Link to the article
A.-K. Späte, H. Bußkamp, A. Niederwieser, V. F. Schart, A. Marx, V. Wittmann
Bioconjug Chem.2014, 25, 147-154
Rapid Labeling of Metabolically Engineered Cell-Surface Glycoconjugates with a Carbamate-Linked Cyclopropene Reporter
Link to the article