Toxin-Based Therapeutic Approaches 英文参考文献.docVIP

Toxins 2010, 2, 2519-2583; doi: 10.3390/toxins2112519 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review Toxin-Based Therapeutic Approaches Assaf Shapira and Itai Benhar * Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel; E-Mail: assafsha@ * Author to whom correspondence should be addressed; E-Mail: benhar@post.tau.ac.il; Tel.: 972-3-6407511; Fax: 972-3-6409407. Received: 14 October 2010; in revised form: 25 October 2010 / Accepted: 26 October 2010 / Published: 28 October 2010 Abstract: Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin. Keywords: toxins; targeting; pseudomonas exotoxin A; diphtheria toxin; ricin; anthrax; immunotoxins; suicide gene 1. Introduction The secretion of polypeptides by prokaryotic and eukaryotic cells is an elaborate mechanism enabling the execution of essential processes like active modulation of the environment, enzymatic processing of nutrients and communication with other cells. However, a unique group of secreted polypeptides, the secreted toxins, plays a different role