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Investigation of the Mechanism of Cytotoxic Natural Product PateamineA analog
Author(s) -
Kommaraju Sai Shilpa,
Low WoonKai,
Romo Daniel
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb114
Subject(s) - natural product , eif4e , eif4a , eif4g , biology , mechanism of action , eukaryotic translation , microbiology and biotechnology , in vitro , biochemistry , stereochemistry , translation (biology) , chemistry , messenger rna , gene
Natural products have served as a source for many modern therapeutics. Over the past decade, high throughput screening of libraries of small molecule compounds have been popular in drug discovery. One such natural product is PateamineA (PatA). The natural product PatA isolated from the marine sponge Mycale hentscheli has been found to be a highly potent antiproliferative agent with potential as a novel anti‐neoplastic agent. PatA and the simplified analog desmethyl, desamino PateamineA (DMDAPatA) have cytotoxicity selective for rapidly proliferating cells by inhibition of cap‐dependent translation initiation through binding to eIF4A (eukaryotic initiation factor 4A) of eIF4F complex. eIF4F complex consists of eIF4A (RNA helicase), eIF4E (cap‐binding protein) and eIF4G (Scaffolding protein). The consequence and impact of other eIF4F complex components on DMDAPatA action are investigated in vitro and and in cultured mammalian cells. Preliminary results demonstrate a role for eIF4E and cap‐binding in DMDAPatA mechanism of action.