These authors contributed equally to this work.
Multivalent Design of Apoptosis-Inducing Bid-BH3 Peptide–Oligosaccharides Boosts the Intracellular Activity at Identical Overall Peptide Concentrations
Article first published online: 4 NOV 2012
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chemistry - A European Journal
Volume 18, Issue 52, pages 16708–16715, December 21, 2012
How to Cite
Richter, M., Chakrabarti, A., Ruttekolk, I. R., Wiesner, B., Beyermann, M., Brock, R. and Rademann, J. (2012), Multivalent Design of Apoptosis-Inducing Bid-BH3 Peptide–Oligosaccharides Boosts the Intracellular Activity at Identical Overall Peptide Concentrations. Chem. Eur. J., 18: 16708–16715. doi: 10.1002/chem.201202276
- Issue published online: 18 DEC 2012
- Article first published online: 4 NOV 2012
- Manuscript Received: 27 JUN 2012
- DFG. Grant Numbers: Ra895–4–6, SFB 765, FOR 806, BR2443–5
- Fonds der Chemischen Industrie
- protein–protein interactions
Multivalent peptide–oligosaccharide conjugates were prepared and used to investigate the multivalency effect concerning the activity of Bid-BH3 peptides in live cells. Dextran oligosaccharides were carboxyethylated selectively in the 2-position of the carbohydrate units and activated for the ligation of N-terminally cysteinylated peptides. Ligation through maleimide coupling was found to be superior to the native chemical ligation protocol. Monomeric Bid-BH3 peptides were virtually inactive, whereas pentameric peptide conjugates induced apoptosis up to 20-fold stronger at identical peptide concentrations. Comparison of lowly multivalent and highly multivalent peptide dextrans proved a multivalency effect in life cells which was specific for the BH3 peptide sequence.