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dc.contributor.author
Grisoni, Francesca
dc.contributor.author
Merk, Daniel
dc.contributor.author
Consonni, Viviana
dc.contributor.author
Hiss, Jan Alexander
dc.contributor.author
Tagliabue, Sara Giani
dc.contributor.author
Todeschini, Roberto
dc.contributor.author
Schneider, Gisbert
dc.date.accessioned
2019-07-12T15:38:13Z
dc.date.available
2018-09-20T08:20:39Z
dc.date.available
2018-09-20T08:54:40Z
dc.date.available
2019-07-12T15:38:13Z
dc.date.issued
2018-08-08
dc.identifier.other
10.1038/s42004-018-0043-x
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/290645
dc.identifier.doi
10.3929/ethz-b-000290645
dc.description.abstract
Natural products offer unexplored molecular frameworks for the development of chemical leads and innovative drugs. However, the structural complexity of natural products compared with synthetic drug-like molecules often limits the scaffold hopping potential of natural-product-inspired molecular design. Here we introduce a holistic molecular representation incorporating pharmacophore and shape patterns, which facilitates scaffold hopping from natural products to isofunctional synthetic compounds. This computational approach captures simultaneously the partial charge, atom distributions and molecular shape. In a prospective application, we use four natural cannabinoids as queries in a chemical database search for novel synthetic modulators of human cannabinoid receptors. Of the synthetic compounds selected by the new method, 35% are experimentally confirmed as active. These cannabinoid receptor modulators are structurally less complex than their respective natural product templates. The results of this study validate this holistic molecular representation for hit and lead finding in drug discovery.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Macmillan Publishers
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Scaffold hopping from natural products to synthetic mimetics by holistic molecular similarity
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
Communications Chemistry
ethz.journal.volume
1
en_US
ethz.journal.issue
1
en_US
ethz.pages.start
44
en_US
ethz.size
9 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
Beyond fragment-based drug design: from natural products to small synthetic mimetics through novel holistic molecular representations
en_US
ethz.identifier.wos
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03852 - Schneider, Gisbert / Schneider, Gisbert
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03852 - Schneider, Gisbert / Schneider, Gisbert
en_US
ethz.grant.agreementno
177477
ethz.grant.fundername
SNF
ethz.grant.funderDoi
10.13039/501100001711
ethz.grant.program
Scientific Exchanges
ethz.date.deposited
2018-09-20T08:20:40Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-09-20T08:54:44Z
ethz.rosetta.lastUpdated
2019-07-12T15:38:23Z
ethz.rosetta.versionExported
true
ethz.COinS
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