Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
TOXICITY OF MYRISTIC ACID ANALOGS TOWARD AFRICAN TRYPANOSOMES
Autore:
DOERING TL; LU TB; WERBOVETZ KA; GOKEL GW; HART GW; GORDON JI; ENGLUND PT;
Indirizzi:
JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM BALTIMORE MD 21205 JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM BALTIMORE MD 21205 WASHINGTON UNIV,SCH MED,DEPT MOLEC BIOL & PHARMACOL ST LOUIS MO 63110
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 21, volume: 91, anno: 1994,
pagine: 9735 - 9739
SICI:
0027-8424(1994)91:21<9735:TOMAAT>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN N-MYRISTOYLTRANSFERASE; SUBSTRATE-SPECIFICITY; COA; BIOSYNTHESIS; ANCHORS; INVITRO; OXYGEN; ASSAY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
17
Recensione:
Indirizzi per estratti:
Citazione:
T.L. Doering et al., "TOXICITY OF MYRISTIC ACID ANALOGS TOWARD AFRICAN TRYPANOSOMES", Proceedings of the National Academy of Sciences of the United Statesof America, 91(21), 1994, pp. 9735-9739

Abstract

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 H-3-labeled oxatetradecanoic acidsto 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/12/20 alle ore 23:38:41