East Bay Coalition for the Homeless: Branding Study and Marketing Strategy

There are a number of potential positioning strategies. The two which make the most sense for the EBCH are to “position the EBCH away from others in the category” and to “position the EBCH as unique.” These strategies have the advantage of setting the EBCH apart from the other organizations that address homelessness. Occupying its own “position” in the minds of potential and current donors is not only an effective communications/marketing strategy but also a less costly one because it avoids head-to-head competition and comparisons

Biology-directed and in silico-aided design liberates a potent, simplified and ipomoeassin-F-derived Sec61 inhibitor

The macrocyclic small molecule inhibitor ipomoeassin F (Ipom-F) binds to the central Sec61α subunit of the Sec61 complex and induces cytotoxicity by disrupting multiple aspects of Sec61-mediated protein biogenesis at the endoplasmic reticulum (ER). Here, we show that the integrity of the Ipom-F macrocycle is not required either for Sec61 inhibition in vitro or the induction of cell death, which is abrogated in cells expressing a resistance-conferring Sec61α mutant. We conclude that Ipom-F and its open-chain analogues interact with Sec61α via its mycolactone binding site and/or lateral gate, thereby occluding the normal Sec61-mediated pathway for membrane protein insertion at the ER. Using biology-directed and in silico-aided design, we have revolutionised the production of Ipom-F to yield open-chain analogue 3; a potent, simplified and synthetically accessible Ipom-F-derived Sec61 inhibitor. We present 3 as a lead compound for the generation of new protein translocation probes and future therapeutic development