Toxicity of myristic acid analogs toward African trypanosomes

Tamara L. Doering, Tianbao Lu, Karl A. Werbovetz, George W. Gokel, Gerald W. Hart, Jeffrey I. Gordon, Paul T. Englund

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


New drugs are needed for treatment of diseases caused by African trypanosomes. One possible target for chemotherapy is the biosynthesis of the glycosyl phosphatidylinositol (GPI) of this parasite's variant surface glycoprotein (VSG). Unlike mammalian GPIs, the diacylglycerol moiety of the VSG anchor contains only myristate (tetradecanoate), added in unique remodeling reactions. We previously found that 11-oxatetradecanoic acid [i.e., 10-(propoxy)decanoic acid] is selectively toxic to trypanosomes. We have now assayed 244 different fatty acid analogs, most with chain lengths comparable to that of myristate, for trypanocidal effects. In these assays we surveyed the effects on toxicity of systematic alterations in the analogs' steric, conformational, and hydrophobic properties. We also used three 3H- labeled oxatetradecanoic acids to explore the mechanism of analog action. Their incorporation into VSG correlated roughly with toxicity, although they also were incorporated into phospholipids and other proteins. Myristate analogs are useful for studying the mechanism of GPI myristoylation, and they are candidates for antitrypanosomal chemotherapy.

Original languageEnglish (US)
Pages (from-to)9735-9739
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number21
StatePublished - Oct 11 1994
Externally publishedYes

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Toxicity of myristic acid analogs toward African trypanosomes'. Together they form a unique fingerprint.

Cite this