Understanding and exploiting nature's chemical arsenal: The past, present and future of calicheamicin research Journal Article
| Authors: | Thorson, J. S.; Sievers, E. L.; Ahlert, J.; Shepard, E.; Whitwam, R. E.; Onwueme, K. C.; Ruppen, M. |
| Article Title: | Understanding and exploiting nature's chemical arsenal: The past, present and future of calicheamicin research |
| Abstract: | The enediyne antitumor antibiotics are appreciated for their novel molecular architecture, their remarkable biological activity and their fascinating mode of action and many have spawned considerable interest as anticancer agents in the pharmaceutical industry. Of equal importance to these astonishing properties, the enediynes also offer a distinct opportunity to study the unparalleled biosyntheses of their unique molecular scaffolds and what promises to be unprecedented modes of self-resistance to highly reactive natural products. Elucidation of these aspects should unveil novel mechanistic enzymology, and may provide access to the rational biosynthetic modification of enediyne structure for new drug leads, the construction of enediyne overproducing strains and eventually lead to an enediyne combinatorial biosynthesis program. This article strives to compile and present the critical research discoveries relevant to the clinically most promising enediyne, calicheamicin, from a historical perspective. Recent progress, particularly in the areas of biosynthesis, self-resistance, bio-engineering analogs and clinical studies are also highlighted. |
| Keywords: | unclassified drug; antineoplastic agent; dna damage; antineoplastic activity; cancer cell culture; drug structure; drug design; drug synthesis; structure activity relation; molecular cloning; cloning, molecular; anti-bacterial agents; dna; drug mechanism; molecular recognition; antibiotics, antineoplastic; structure analysis; antineoplastic antibiotic; dna cleavage; gemtuzumab ozogamicin; aminoglycosides; alkynes; bioengineering; alkenes; calicheamicin; priority journal; article; methymycin; pikromycin; esperamicin; calicheamicin derivative; cmb 401; micromonospora; partial drug synthesis |
| Journal Title: | Current Pharmaceutical Design |
| Volume: | 6 |
| Issue: | 18 |
| ISSN: | 1381-6128 |
| Publisher: | Bentham Science Publishers |
| Date Published: | 2000-01-01 |
| Start Page: | 1841 |
| End Page: | 1879 |
| Language: | English |
| PUBMED: | 11102565 |
| PROVIDER: | scopus |
| DOI: | 10.2174/1381612003398564 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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