DIFFERENTIAL INHIBITION OF FUNGAL OXIDOSQUALENE CYCLASE BY 6E-ISOMER AND 6Z-ISOMER OF 2,3-EPOXY-10-AZA-10,11-DIHYDROSQUALENE

被引：15

作者：

BALLIANO, G

MILLA, P

CERUTI, M

VIOLA, F

CARRANO, L

CATTEL, L

机构：

[1] IST CHIM FARMACEUT APPLICATA, CORSO RAFFAELLO 31, I-10125 TURIN, ITALY

[2] MMDRI, LEPETIT RES CTR, I-21040 GERENZANO, ITALY

来源：

FEBS LETTERS | 1993年 / 320卷 / 03期

关键词：

OXIDOSQUALENE CYCLASE; STEROL BIOSYNTHESIS INHIBITOR; SACCHAROMYCES-CEREVISIAE; CANDIDA-ALBICANS;

D O I：

10.1016/0014-5793(93)80586-J

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Inhibitory properties of 6E (compound 1) and 6Z (compound 2) isomers of 2,3-epoxy-10-aza-10,11-dihydrosqualene against oxidosqualene-lanosterol cyclase were assayed on microsomes and whole cells of Saccharomyces cerevisiae and Candida albicans. Only the 6E isomer (compound 1), bearing a correct substrate-like configuration, strongly inhibited the enzyme both in microsomes and cell cultures. The difference between compounds 1 and 2 (which had an unfavorable geometry) was especially evident when measuring [C-14]acetate incorporation into non-saponifiable lipids extracted from treated cells. While isomer Z was totally ineffective at up to 30 muM, in cells treated with 5 muM isomer E, labelled oxidosqualene, the level of which was negligible in the control, rose to over 60% of the non-saponifiable lipids.

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页码：203 / 206

页数：4

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