title: Multivalent design of apoptosis-inducing bid-BH3 peptide-oligosaccharides boosts the intracellular activity at identical overall peptide concentrations.
abstract: 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.
authors.affiliation: Leibniz Institut für Molekulare Pharmakologie, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Richter
authors.forename: Alokta
authors.initials: A
authors.lastname: Chakrabarti
authors.forename: Ivo R
authors.initials: IR
authors.lastname: Ruttekolk
authors.forename: Burkhard
authors.initials: B
authors.lastname: Wiesner
authors.forename: Michael
authors.initials: M
authors.lastname: Beyermann
authors.forename: Roland
authors.initials: R
authors.lastname: Brock
authors.forename: Jörg
authors.initials: J
authors.lastname: Rademann
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000737:chemistry*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003911:Dextrans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018274:Electroporation; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008301:Maleimides / Q000737:chemistry; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000737:chemistry; D010446:Peptide Fragments / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013050:Spectrometry, Fluorescence
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C474007:Bax protein (53-86); D003911:Dextrans; D008301:Maleimides; D009842:Oligopeptides; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; C491427:nonaarginine; C043592:maleimide