Cellular delivery of therapeutics using the bacterial protein toxin subunit Shiga-B

ORGN 321

Jean-Claude Florent, Jean-Claude.Florent@curie.fr, Centre de recherche, Institut Curie, 26 rue d’Ulm, Paris, F-75248, France
Targeted drug delivery is a major goal of chemotherapy. Its achievement is clearly a significant challenge. One possibility is to take advantage of the various receptor-mediated endocytic pathways operating in a particular cell. The expression of globotriaosylceramide or Gb3 is enhanced in various cancers relative to expression in the corresponding normal tissue. This has led to the development of strategies that utilize its natural ligand the protein Shiga toxin (STxB) to target these cancerous tissues. Its retrograde trafficking pathway from endosomes to the Golgi apparatus and endoplasmic reticulum is of special importance since it provides a route to deliver drugs bypassing the acid pH and hydrolytic environment of the lysosome. The non toxic B-subunit of shiga toxin (STxB) has been modified by incorporating a terminal cystein (STxB-SH) to prepare conjugates of two important drugs for drug delivery; the pro-apoptotic benzodiazepine RO5-4864 which ligand of the peripheral benzodiazepine receptor and the topoisomerase I inhibitor SN-38.
 

Small Molecule Therapeutic Agents
8:30 AM-11:50 AM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- 207A, Oral

Division of Organic Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009