Jump to main content
Jump to site search

Issue 2, 2013
Previous Article Next Article

Novel FK506 and FK520 analogues via mutasynthesis: mutasynthon scope and product characteristics

Author affiliations

Abstract

Novel FK506 and FK520 analogues were generated via biosynthetic engineering in order to generate analogue compounds with equal potency but improved pharmacological profiles compared to FK506. Strains suitable for mutasynthesis were produced by abolishing the activity of the rapK homolog fkbO, thereby disabling starter unit biosynthesis, and by replacing the polyketide synthase loading modules with the AT–ACP didomain equivalent from the avermectin PKS. A test set of FK506 and FK520 analogues was prepared and assessed for potency, physicochemical properties and pharmacokinetics, revealing that these compounds retain potency but are otherwise differentiated from the parent compounds.

Graphical abstract: Novel FK506 and FK520 analogues via mutasynthesis: mutasynthon scope and product characteristics

Back to tab navigation

Supplementary files

Publication details

The article was received on 07 Sep 2012, accepted on 09 Nov 2012 and first published on 21 Nov 2012


Article type: Concise Article
DOI: 10.1039/C2MD20266B
Citation: Med. Chem. Commun., 2013,4, 324-331
  •   Request permissions

    Novel FK506 and FK520 analogues via mutasynthesis: mutasynthon scope and product characteristics

    S. J. Moss, A. E. Stanley-Smith, U. Schell, N. J. Coates, T. A. Foster, S. Gaisser, M. A. Gregory, C. J. Martin, M. Nur-e-Alam, M. Piraee, M. Radzom, D. Suthar, D. G. Thexton, T. D. Warneck, M. Zhang and B. Wilkinson, Med. Chem. Commun., 2013, 4, 324
    DOI: 10.1039/C2MD20266B

Search articles by author

Spotlight

Advertisements