Chemical Precision Tools to Dissect Protein Glycosylation

Datum

11.06.2026

Zeit

11:00 - 12:00

Sprecher

Benjamin Schumann

Zugehörigkeit

TU Dresden

Serie

MPI-CBG Thursday Seminar

Sprache

en

Hauptthema

Biologie

Host

André Nadler

Beschreibung

Alterations in glycoprotein expression and composition are an undisputed corollary of developmental processes, host-pathogen interactions and cancer formation. Consequently, some of the most important tumor biomarkers are heavily glycosylated. Understanding cellular glycoproteome changes is paramount but hampered by experimental limitations. Protein glycosylation is mediated by the activities of >200 glycosyltransferases mainly located in the secretory pathway. Since these transferases are interdependent through compensation and competition, traditional methods of molecular cell biology fail to fully address the complexity of glycoprotein biosynthesis. Furthermore, workflows in mass spec-glycoproteome analysis are often restricted to isolated cell lines that do not adequately reflect the interactions within tissues or between tumor and microenvironment. Thus, we lack strategies to understand 1) the protein substrate specificities of individual glycosyltransferases and 2) which glycoproteins are made by cells in response to their microenvironment. We also 3) miss chemical probes to investigate and disrupt cancer-relevant glycosylation. Here, I describe our development of chemical “Precision Tools” to dissect cellular glycosylation. We employ bump-and-hole (BH) engineering to render glycosyltransferases receptive to a chemically modified nucleotide-sugar substrate that carries a bioorthogonal tag and is not used by wildtype transferases. Engineering individual transferases allows differential profiling of their protein substrate specificities. We found that establishing cellular BH systems required innovation in the delivery of corresponding nucleotide-sugarsto the secretory pathway. We have also taken initiative in the development of small molecule inhibitors against cancer-relevant glycosylation enzymes. Thus, chemical Precision Tools allow us to profile protein glycosylation as a key player in cancer biology.

Letztmalig verändert: 11.06.2026, 07:37:20