CHARACTERIZATION OF N-MYRISTOYL TRANSFERASE INHIBITORS AND THEIR EFFECT ON HIV RELEASE

被引:20
作者
SAERMARK, T
KLEINSCHMIDT, A
WULFF, AM
ANDREASSEN, H
MAGEE, A
ERFLE, V
机构
[1] GESELL STRAHLEN & UMWELTFORSCH MBH, MOLEK ZELLPATHOL ABT, W-8042 NEUHERBERG, GERMANY
[2] NATL INST MED RES, EUCARYOT MOLEC GENET LAB, LONDON NW7 1AA, ENGLAND
关键词
ACYLATION; N-MYRISTOYL TRANSFERASE; MYRISTOYLATION; HIV RELEASE;
D O I
10.1097/00002030-199108000-00005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Acylation of virus proteins is an important covalent modification which has been shown, in many cases, to be necessary for their normal function. Furthermore, it has been shown that cerulenin, an inhibitor of this process, inhibits formation of vesicular stomatitis virus and Rous sarcoma virus in infected cultures, as well as acylation of HIV proteins. However, in agreement with earlier reports, we found that the acylating enzyme, N-myristoyl transferase, was unaffected by cerulenin which did, however, inhibit protein synthesis, thereby making interpretation of its effects difficult. Analogues of myristic acid were found to inhibit acylation in intact cells without toxic effects on protein synthesis or mitochondrial function. Myristic acid analogues were also shown by an in vitro assay to act directly on the acylating activity (N-myristoyl transferase). Furthermore, myristic acid analogues were found to inhibit HIV release from HIV-infected cells and glucosamine, which has recently been shown to be a non-competitive inhibitor of N-myristoyl-transferase, also inhibited HIV release.
引用
收藏
页码:951 / 958
页数:8
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