Hoepfner, Dominic, Krastel, Philipp, Schirle, Markus, Schmitt, Esther and Roggo, Silvio (2015) Nannocystin A: an Elongation Factor 1 Inhibitor from Myxobacteria with Differential Anti-Cancer Properties. Angewandte Chemie Int Edition, 54 (35). pp. 10149-10154. ISSN 14337851

Abstract

Cultivation of myxobacteria of the Nannocystis genus led to the isolation and structure elucidation of a novel class of cyclic lactone compounds 1-6. Whole genome sequence analysis and annotation enabled identification of the putative biosynthetic cluster and synthesis process. In biological assays the compounds displayed anti-fungal and cytotoxic activity. Combined genetic and proteomic approaches identified the eukaryotic translation elongation factor 1 (EF-1) as the primary target for this compound class that we thus propose to name elongolides. Elongolide A2 (1) displayed differential activity across various cancer cell lines and EEF1A1 expression levels appear to be the main differentiating factor. Biochemical and genetic evidence support an overlapping binding site with the anti-cancer compound didemin B on EF-1. Elongolides thus offer an interesting starting point for further investigations of the potential of therapeutics targeting elongation factor 1.

Item Type:	Article
Date Deposited:	25 Apr 2016 23:45
Last Modified:	04 Jul 2016 23:45
URI:	https://oak.novartis.com/id/eprint/25910