In our continued efforts towards probing the physiologically relevant protein binding partners of the phenanthrolizidine alkaloids, we wish to report the design and synthesis of a biotinylated derivative of the tylophorine analog DCB-3503 bearing a novel tether. The interaction between a molecular probe and its target is typically governed by variables such as linker length and composition; as such, we chose to incorporate a PEG-based linker of exceptional length, between the active head unit and the biotin moiety. Attachment of a heterobifunctional PEG derivative to the phenanthrene skeleton of DCB-3503 followed by �click� conjugation with PEG-functionalized biotin facilitated access to the target probe. Modeling studies indicated that a significant portion (21.365 �) of the DCB-3503-biotin conjugate remained sufficiently exposed even after simulated streptavidin capture, making it suitable for targeting any potentially elusive binding partners. Furthermore, owing to its exceptional length and enhanced hydrophilicity, this novel tether may find uses in other applications such as drug delivery.                                                     

Synthesis of a biotin conjugate of the tylophorine analog DCB-3503 bearing a novel PEG-based tether

242nd National Meeting (2011)

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