An analog of myristic acid with selective toxicity for African trypanosomes.
Trypanosoma brucei, the protozoan parasite responsible for African sleeping sickness, evades the host immune response through the process of antigenic variation. The variant antigen, known as the variant surface glycoprotein (VSG), is anchored to the cell surface by a glycosyl phosphatidylinositol (GPI) structure that contains myristate (n-tetradecanoate) as its only fatty acid component. The utilization of heteroatom-containing analogs of myristate was studied both in a cell-free system and in vivo. Results indicated that the specificity of fatty acid incorporation depends on chain length rather than on hydrophobicity. One analog, 10-(propoxy)decanoic acid, was highly toxic to trypanosomes in culture although it is nontoxic to mammalian cells.
Doering
T L
TL
Department of Biological Chemistry, Johns Hopkins Medical School, Baltimore, MD 21210.
Raper
J
J
Buxbaum
L U
LU
Adams
S P
SP
Gordon
J I
JI
Hart
G W
GW
Englund
P T
PT
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002474:Cell-Free System; D006017:Glycolipids / Q000378:metabolism; D017261:Glycosylphosphatidylinositols; D007700:Kinetics; D051379:Mice; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism* / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D013329:Structure-Activity Relationship; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D000214:Acyl Coenzyme A; D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D009227:Myristic Acids; D010716:Phosphatidylinositols; D019814:Myristic Acid; C060254:10-propoxydecanoic acid; C069607:10-(propoxy)decanoyl-coenzyme A; C040349:S-tetradecanoyl-coenzyme A