Synthesis and Investigation of -Substituted 2-Mercaptobenzoimidazoles as Inhibitors of Hedgehog Signaling.

Due to the arising resistance of common drugs targeting the Hedgehog signaling pathway, the identification of new compound classes with inhibitory effect is urgently needed. We were able to identify -alkylated 2-mercaptobenzoimidazoles as a new compound class that exhibits Hedgehog signaling activity in a low micromolar range. The scope of the 2-mercaptobenzoimidazole motif has been investigated by the syntheses of diverse derivatives, revealing that the elongation of the linker unit and the exchange of particular substitution patterns are tolerable with respect to the activity of the compound class.

Cell Penetrating Peptoids (CPPos): Synthesis of a Small Combinatorial Library by Using IRORI MiniKans.

Cell penetrating peptoids (CPPos) are potent mimics of the corresponding cell penetrating peptides (CPPs). The synthesis of diverse oligomeric libraries that display a variety of backbone scaffolds and side-chain appendages are a very promising source of novel CPPos, which can be used to either target different cellular organelles or even different tissues and organs. In this study we established the submonomer-based solid phase synthesis of a "proof of principle" peptoid library in IRORI MiniKans to expand the amount for phenotypic high throughput screens of CPPos.