1521-3773/asset/2002_left.gif?v=1&s=ac6b0d94a94d7ce7a210002b8096b42feffc0bcf)
1521-3773/asset/olbannercenter.gif?v=1&s=c083e1920cd41ed129901c116018eab93b5ad3c4)
1521-3773/asset/2002_right.gif?v=1&s=451042aa3415ae3ad0729984d26dee1866aca82e)
Review
Biology-Oriented Synthesis
Article first published online: 28 OCT 2011
DOI: 10.1002/anie.201007004
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Issue
Angewandte Chemie International Edition
Volume 50, Issue 46, pages 10800–10826, November 11, 2011
Additional Information
How to Cite
Wetzel, S., Bon, R. S., Kumar, K. and Waldmann, H. (2011), Biology-Oriented Synthesis. Angew. Chem. Int. Ed., 50: 10800–10826. doi: 10.1002/anie.201007004
Publication History
- Issue published online: 9 NOV 2011
- Article first published online: 28 OCT 2011
- Manuscript Received: 8 NOV 2010
Funded by
- Max-Planck-Gesellschaft
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Alexander von Humboldt-Stiftung
- Volkswagen-Stiftung
- European Union. Grant Numbers: FP7/2007-2013, 268309
- Land Nordrhein-Westfalen
- Fonds der Chemischen Industrie
- Abstract
- Article
- References
- Cited By
Keywords:
- bioorganic chemistry;
- chemoinformatics;
- medicinal chemistry;
- natural products;
- synthesis design
Abstract
Which compound classes are best suited as probes and tools for chemical biology research and as inspiration for medicinal chemistry programs? Chemical space is enormously large and cannot be exploited conclusively by means of synthesis efforts. Methods are required that allow one to identify and map the biologically relevant subspaces of vast chemical space, and serve as hypothesis-generating tools for inspiring synthesis programs. Biology-oriented synthesis builds on structural conservatism in the evolution of proteins and natural products. It employs a hierarchical classification of bioactive compounds according to structural relationships and type of bioactivity, and selects the scaffolds of bioactive molecule classes as starting points for the synthesis of compound collections with focused diversity. Navigation in chemical space is facilitated by Scaffold Hunter, an intuitively accessible and highly interactive software. Small molecules synthesized according to BIOS are enriched in bioactivity. They facilitate the analysis of complex biological phenomena by means of acute perturbation and may serve as novel starting points to inspire drug discovery programs.