Monday, July 27, 2009 - 3:05 PM
S49

Enediyne antitumor antibiotics: Discovery and therapeutic potential

Frank E. Koehn, Haiyin He, Haltli Brad, Leighton Margaret, Feng Xidong, Yang Hui, Bernan Valerie, Janso Jeffrey, and Charan Romila. Natural Products Discovery- Chemical Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10990

The enediyne antitumor antibiotics have been the subject of inspired chemical and biological research for more than two decades.  The elegant chemical structures, molecular mechanism and biosynthesis of these fascinating molecules, combined with their exquisite potency, have led several laboratories to investigate their utility as drug candidates. Driven by the therapeutic success of the first-in-class calicheamicin antibody conjugate Mylotarg™, and CMC-544, an CD22-targeted calicheanmicin immunoconjugate currently in clinical trial, we have maintained an ongoing interest in isolating new enediyne antibiotics, and in understanding the micro-organisms which produce them. In this talk, we describe recent results from our laboratory, which include the isolation and characterization of a nine-member enediyne chromoprotein complex isolated from the culture broth of an Actinomadura sp., and studies directed toward identifying additional enediynes from marine actinomycetes.