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'''Chemical postevolution''' is the structural optimization of (already evolutionary optimized) [[natural product]]s by synthetic chemical means. It is additional and often structurally orthogonal to natural [[evolution]].<ref> F. von Nussbaum, M. Brands, B. Hinzen, S. Weigand, D. Häbich, ''Angew. Chem.'' '''2006''', ''118'', 5194–5254; ''Angew. Chem. Int. Ed.'' '''2006''', ''45'', 5072–5129. Antibacterial Natural Products in Medicinal Chemistry—Exodus or Revival? PMID 16881035</ref> Whereas the term "[[Chemical Evolution]]" refers to an iterative optimization of any possible chemical structure, the term Chemical Postevolution especially refers to the biological improvement of antibiotic natural products by synthetic organic chemistry, primarily in antiinfective and anticancer research.<br />
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== Application in drug discovery == <br />
Natural products have provided the majority of [[lead structure]]s for marketed [[antibiotics]].<ref> C. Walsh, Antibiotics, actions, origins, resistance, 1. Aufl., ASM,<br />
Washington, DC, 2003</ref> But, only a few “pure” natural products fulfill the complex profile required for a pharmaceutical drug. A drug has to match additional physicochemical, pharmacological, toxicological and technical requirements that have not been selectors in the evolution of antibacterial [[secondary metabolites]]. On the other hand, natural products offer excellent starting points for medicinal chemistry. To create a drug, nature’s blueprints often have to be improved by [[semisynthesis]] or [[de novo synthesis]] to repair typical deficiencies such as limited stability, low solubility, narrow [[antibacterial spectrum]], poor in vivo efficacy, etc. Chemical structure defines biological activity. Complementary to nature, a chemist can explore white spots in structural space and biological activity that have never been explored by any organism over the entire period of evolution.<br />
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== Examples == <br />
Various natural antibiotics have already been optimized. Classical examples are the beta-lactam antibiotics (e.g. [[penicillin G]] to [[meticillin]]), the glycopeptides ([[chloroeremomycin]] to [[oritavancin]]) or the macrolides ([[erythromycin]] A to [[telithromycin]]). Since 2006 [[platensimycin]].<ref name=Wang2006>Jun Wang ''et al'', ''Platensimycin is a selective FabF inhibitor with potent antibiotic properties'', Nature 441, 358-361 (18 May 2006) PMID 16710421</ref> has been the target for various synthetic studies aiming at a chemical postevolution of this potent FabF inhibitor. Various other classes of natural antibiotics are now in the focus of chemical postevolution.<ref> K. C. Nicolaou, Jason S. Chen, David J. Edmonds, Anthony A. Estrada, ''Angew. Chem.'' '''2009''', ''121'', 670–732; ''Angew. Chem. Int. Ed.'' '''2009''', ''48'', 660-719. Recent Advances in the Chemistry and Biology of Naturally Occurring Antibiotics <br />
PMID 19130444</ref><br />
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== References == <br />
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[[Category:Biotechnology products]]</div>80.132.83.105