Derek D. Doorneweerd

Synthesis and activity of folate conjugated didemnin B for potential treatment of inflammatory diseases.

A folate receptor targeted didemnin B conjugate was synthesized using a hydrophilic peptide spacer linked to folate via a releasable disulfide carbonate linker. Cell cytotoxicity and TNF-α inhibition in RAW264.7 macrophage-like cells exhibited IC(50)s of 13 and 5 nM, respectively. Folate didemnin B was found to be ∼50-100 fold more potent than didemnin B itself. More importantly, activity of the prodrug was blocked by excess folic acid, demonstrating receptor-mediated cellular uptake of the conjugate.

Sensing of Bacillus Subtilis Spores with Peptide Functionalized Microcantilevers

Short peptide ligands were synthesized to selectively capture spores using microcantilever arrays. Our initial studies focused on the capture of Bacillus subtilis (a stimulant of Bacillus anthracis) spores in liquids. A peptide-ligand-functionalized microcantilever array was mounted on a flow cell filled with a B. subtilis suspension while cantilever deflection was monitored. Also, fifth mode resonant frequency measurements were performed before and after dipping a peptide-ligand-functionalized microcantilever array in a static B. subtilis solution. Both techniques showed selective binding to functionalized cantilevers when compared to arrays functionalized with a similar control (non-binding) peptide. Conclusive confirmation of selective binding was obtained by subsequent examination of the microcantilever arrays under a dark field microscope. The concentration sensitivity, shelf-life of the binding ligands, and their binding efficiency were studied as well.