Natural products targeting the elongation phase of eukaryotic protein biosynthesis.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractCovering: 2000 to 2020 The translation of mRNA into proteins is a precisely regulated, complex process that can be divided into three main stages, i.e. initiation, elongation, termination, and recycling. This contribution is intended to highlight how natural products interfere with the elongation phase of eukaryotic protein biosynthesis. Cycloheximide, isolated from Streptomyces griseus, has long been the prototype inhibitor of eukaryotic translation elongation. In the last three decades, a variety of natural products from different origins were discovered to also address the elongation step in different manners, including interference with the elongation factors eEF1 and eEF2 as well as binding to A-, P- or E-sites of the ribosome itself. Recent advances in the crystallization of the ribosomal machinery together with natural product inhibitors allowed characterizing similarities as well as differences in their mode of action. Since aberrations in protein synthesis are commonly observed in tumors, and malfunction or overexpression of translation factors can cause cellular transformation, the protein synthesis machinery has been realized as an attractive target for anticancer drugs. The therapeutic use of the first natural products that reached market approval, plitidepsin (Aplidin®) and homoharringtonine (Synribo®), will be introduced. In addition, we will highlight two other potential indications for translation elongation inhibitors, i.e. viral infections and genetic disorders caused by premature termination of translation.
CitationNat Prod Rep. 2020 Jun 24;37(6):752-762. doi: 10.1039/d0np00011f.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
PublisherRoyal Society of Chemistry
JournalNatural product reports
The following license files are associated with this item:
- Creative Commons
- Inhibition of eukaryotic translation elongation by the antitumor natural product Mycalamide B.
- Authors: Dang Y, Schneider-Poetsch T, Eyler DE, Jewett JC, Bhat S, Rawal VH, Green R, Liu JO
- Issue date: 2011 Aug
- Eukaryotic translation elongation factor 2 (eEF2) catalyzes reverse translocation of the eukaryotic ribosome.
- Authors: Susorov D, Zakharov N, Shuvalova E, Ivanov A, Egorova T, Shuvalov A, Shatsky IN, Alkalaeva E
- Issue date: 2018 Apr 6
- RNA helicase DDX19 stabilizes ribosomal elongation and termination complexes.
- Authors: Mikhailova T, Shuvalova E, Ivanov A, Susorov D, Shuvalov A, Kolosov PM, Alkalaeva E
- Issue date: 2017 Feb 17
- Versatile Synthetic Route to Cycloheximide and Analogues That Potently Inhibit Translation Elongation.
- Authors: Park Y, Koga Y, Su C, Waterbury AL, Johnny CL, Liau BB
- Issue date: 2019 Apr 8
- Some properties and the possible role of intrinsic ATPase of rat liver 80S ribosomes in peptide bond elongation.
- Authors: Ogata K, Ohno R, Terao K, Iwasaki K, Endo Y
- Issue date: 2000 Feb