Karageorgis, G orcid.org/0000-0001-5088-6047, Foley, DJ, Laraia, L et al. (1 more author) (2020) Principle and design of pseudo-natural products. Nature Chemistry, 12 (3). pp. 227-235. ISSN 1755-4330
Abstract
Natural products (NPs) are a significant source of inspiration towards the discovery of new bioactive compounds based on novel molecular scaffolds. However, there are currently only a small number of guiding synthetic strategies available to generate novel NP-inspired scaffolds, limiting both the number and types of compounds accessible. In this Perspective, we discuss a design approach for the preparation of biologically relevant small-molecule libraries, harnessing the unprecedented combination of NP-derived fragments as an overarching strategy for the synthesis of new bioactive compounds. These novel ‘pseudo-natural product’ classes retain the biological relevance of NPs, yet exhibit structures and bioactivities not accessible to nature or through the use of existing design strategies. We also analyse selected pseudo-NP libraries using chemoinformatic tools, to assess their molecular shape diversity and properties. To facilitate the exploration of biologically relevant chemical space, we identify design principles and connectivity patterns that would provide access to unprecedented pseudo-NP classes, offering new opportunities for bioactive small-molecule discovery.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © Springer Nature Limited 2020. This is an author produced version of a paper published in Nature Chemistry. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Organic Chemistry (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 Mar 2020 13:51 |
Last Modified: | 03 Aug 2020 00:41 |
Status: | Published |
Publisher: | Nature Research |
Identification Number: | 10.1038/s41557-019-0411-x |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:158147 |