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  From protein domains to drug candidates - Natural products as guiding principles in the design and synthesis of compound libraries

Breinbauer, R.-P., Vetter, I. R., & Waldmann, H. (2002). From protein domains to drug candidates - Natural products as guiding principles in the design and synthesis of compound libraries. Angewandte Chemie - International Edition, 41(16): 1, pp. 2879-2890. Retrieved from http://dx.doi.org/10.1002/1521-3773(20020816)41:16<2878:AID-ANIE2878>3.0.CO;2-B.

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Genre: Journal Article
Alternative Title : Angew. Chem.-Int. Edit.

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 Creators:
Breinbauer, Rolf-Peter1, Author           
Vetter, Ingrid R.2, Author           
Waldmann, Herbert1, Author           
Affiliations:
1Abt. IV: Chemische Biologie, Max Planck Institute of Molecular Physiology, Max Planck Society, ou_1753290              
2Abt. I:Mechanistische Zellbiologie, Max Planck Institute of Molecular Physiology, Max Planck Society, ou_1753287              

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Free keywords: bioorganic chemistry; combinatorial chemistry; natural products; protein structures; solid-phase synthesis
 Abstract: In the continuing effort to find small molecules that alter protein function and ultimately might lead to new drugs, combinatorial chemistry has emerged as a very powerful tool. Contrary to original expectations that large libraries would result in the discovery of many hit and lead structures, it has been recognized that the biological relevance, design, and diversity of the library are more important. As the universe of conceivable compounds is almost infinite, the question arises: where is a biologically validated starting point from which to build a combinatorial library? Nature itself might provide an answer: natural products have been evolved to bind to proteins. Recent results in structural biology and bioinformatics indicate that the number of distinct protein families and folds is fairly limited. Often the same structural domain is used by many proteins in a more or less modified form created by divergent evolution. Recent progress in solid-phase organic synthesis has enabled the synthesis of combinatorial libraries based on the structure of complex natural products. It can be envisioned that natural-product-based combinatorial synthesis may permit hit or lead compounds to be found with enhanced probability and quality.

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Language(s): eng - English
 Dates: 2002
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: Angewandte Chemie - International Edition
  Alternative Title : Angew. Chem.-Int. Edit.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 41 (16) Sequence Number: 1 Start / End Page: 2879 - 2890 Identifier: -