Core supports the studies of the five COBRE projects and Core by: 1) preparing libraries for screening and lead optimization; 2) synthesizing organizing compounds; 3) providing extracts fro natural products; 4) preparing affinity labels. Specifically, a radioactive daunomycin photoaffinity analogue will be prepared (Project, Suprenant); a library of kinase inhibitors will be prepared which will be investigated to identify: a) a) src kinase inhibitory activity (Project, Roby), cyclin-dependent kinase inhibition (Project, Quackenbush), ERK1/2 inhibition (Project, Persons). Depending on the outcome of the studies, lead optimization will be initiated. Core will also be actively involved in the design and synthesis of the H2- receptor agonist libraries and the tetraspanin mimics (Proposal, Todd). Core will also take the lad in compound acquisition for screening in Core. This will involve local synthetic compounds and extracts of natural products, compounds from the NCI repository of synthetic and natural products plant-derived extracts from collaborators in Costa Rica, and extracts from a collection of 400 myxobacteria species. In addition, Core will carry out the synthesis of a potentially promising novel anti-tumor agent, octalactin A, to assess its potential for cancer therapy.
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