Jump to main content
Jump to site search

Issue 32, 2016
Previous Article Next Article

Biosynthesis-driven structure–activity relationship study of premonensin-derivatives

Author affiliations

Abstract

The controlled derivatization of natural products is of great importance for their use in drug discovery. The ideally rapid generation of compound libraries for structure–activity relationship studies is of particular concern. We here use modified biosynthesis for the generation of such a library of reduced polyketides to interfere with the oncogenic KRas pathway. The polyketide is derivatized via side chain alteration, and variations in its redox pattern and in its backbone chain length through manipulation in the corresponding polyketide synthase. Structural and biophysical analyses revealed the nature of the interaction between the polyketides and KRas-interacting protein PDE6δ. Non-natural polyketides with low nanomolar affinity to PDE6δ were identified.

Graphical abstract: Biosynthesis-driven structure–activity relationship study of premonensin-derivatives

Back to tab navigation

Supplementary files

Publication details

The article was received on 02 Jun 2016, accepted on 15 Jul 2016 and first published on 19 Jul 2016


Article type: Paper
DOI: 10.1039/C6OB01201A
Citation: Org. Biomol. Chem., 2016,14, 7671-7675
  • Open access: Creative Commons BY license
  •   Request permissions

    Biosynthesis-driven structure–activity relationship study of premonensin-derivatives

    A. Ismail-Ali, E. K. Fansa, N. Pryk, S. Yahiaoui, S. Kushnir, M. Pflieger, A. Wittinghofer and F. Schulz, Org. Biomol. Chem., 2016, 14, 7671
    DOI: 10.1039/C6OB01201A

    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements