Multivalent Design of Apoptosis-Inducing Bid-BH3 Peptide-Oligosaccharides Boosts the Intracellular Activity at Identical Overall Peptide Concentrations
Multivalent Design of Apoptosis-Inducing Bid-BH3 Peptide-Oligosaccharides Boosts the Intracellular Activity at Identical Overall Peptide Concentrations
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DOI：
10.1002/chem.201202276
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发表时间：
2012-12-01
影响因子：
4.3
通讯作者：
Rademann, Joerg
中科院分区：
文献类型：
--
作者：
Richter, Martin;Chakrabarti, Alokta;Rademann, Joerg
制备多价肽寡糖缀合物并用于研究关于Bid-BH 3肽在活细胞中的活性的多价效应。葡聚糖寡糖在碳水化合物单元的2-位被选择性地羧乙基化，并被激活用于连接N-末端半胱氨酸化肽。发现通过马来酰亚胺偶联的连接上级天然化学连接方案。单体Bid-BH 3肽几乎是无活性的，而五聚体肽缀合物在相同的肽浓度下诱导细胞凋亡高达20倍。低多价和高多价肽葡聚糖的比较证明了在生命细胞中对BH 3肽序列特异的多价效应。
Multivalent peptideoligosaccharide 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.