Inhibitory effects of pentamidine analogues on protein biosynthesis in vitro

被引：10

作者：

Bielawski, K ^{[1
]}

Galicka, A

Bielawska, A

Sredzinska, K

机构：

[1] Med Acad Bialystok, Inst Chem, Dept Med Chem & Drug Technol, PL-15230 Bialystok 8, Poland

[2] Med Acad Bialystok, Inst Chem, Dept Gen & Organ Chem, PL-15230 Bialystok, Poland

来源：

ACTA BIOCHIMICA POLONICA | 2000年 / 47卷 / 01期

关键词：

amidine; DAPI; protein synthesis in vitro; elongation factors;

D O I：

10.18388/abp.2000_4068

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：

Pentamidine despite its rather high toxicity, is currently in clinical use. For development of new drugs of this type it. is important to know the mechanism of their action. Two new amidines (I and II) and 4',6-diamidino-2-phenylindole (DAPI) were found in preliminary experiments to inhibit protein synthesis in vitro in the cell-free rat liver system. The three compounds differed in the precise mode of action. The inhibitory effect of I on the activity of the eukaryotic elongation factor eEF-2 and ribosomes seems to suggest that the binding site of eEF-2 on the ribosome was blocked by this compound, eEF-2 has been identified as the primary target of II and eEF-1 as the primary target of DAPI in the system studied.

引用

页码：113 / 120

页数：8

共 26 条

[1] STRUCTURE-ACTIVITY-RELATIONSHIPS OF ANALOGS OF PENTAMIDINE AGAINST PLASMODIUM-FALCIPARUM AND LEISHMANIA-MEXICANA-AMAZONENSIS [J].

BELL, CA ;

HALL, JE ;

KYLE, DE ;

GROGL, M ;

OHEMENG, KA ;

ALLEN, MA ;

TIDWELL, RR .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1990, 34 (07) :1381-1386

[2] INHIBITION OF CRYPTOSPORIDIUM-PARVUM IN NEONATAL HSD-(ICR)BR SWISS MICE BY POLYETHER IONOPHORES AND AROMATIC AMIDINES [J].

BLAGBURN, BL ;

SUNDERMANN, CA ;

LINDSAY, DS ;

HALL, JE ;

TIDWELL, RR .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1991, 35 (07) :1520-1523

[3] STRUCTURE AND DNA-BINDING ACTIVITY OF ANALOGS OF 1,5-BIS(4-AMIDINOPHENOXY)PENTANE (PENTAMIDINE) [J].

CORY, M ;

TIDWELL, RR ;

FAIRLEY, TA .

JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (03) :431-438

[4] STRUCTURE, DNA MINOR-GROOVE BINDING, AND BASE-PAIR SPECIFICITY OF ALKYL-LINKED AND ARYL-LINKED BIS(AMIDINOBENZIMIDAZOLES) AND BIS(AMIDINOINDOLES) [J].

FAIRLEY, TA ;

TIDWELL, RR ;

DONKOR, I ;

NAIMAN, NA ;

OHEMENG, KA ;

LOMBARDY, RJ ;

BENTLEY, JA ;

CORY, M .

JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (12) :1746-1753

[5] FOOTPRINTING STUDIES ON THE SEQUENCE-SELECTIVE BINDING OF PENTAMIDINE TO DNA [J].

FOX, KR ;

SANSOM, CE ;

STEVENS, MFG .

FEBS LETTERS, 1990, 266 (1-2) :150-154

[6] MULTIFORMITY OF ELONGATION-FACTOR EEF-2 ISOLATED FROM RAT-LIVER CELLS [J].

GAJKO, A ;

GALASINSKI, W ;

GINDZIENSKI, A .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 202 (02) :844-849

[7]

GALASINSKI W, 1969, J BIOL CHEM, V244, P6527

[8] PNEUMOCYSTIS-CARINII PNEUMONIA AND ITS TREATMENT IN PATIENTS WITH AIDS [J].

GAZZARD, BG .

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1989, 23 :67-75

[9]

JABLONOWSKA K, 1983, ACTA BIOCHIM POL, V30, P381

[10] BINDING OF AN ANTITUMOR DRUG TO DNA NETROPSIN AND C-G-C-G-A-A-T-T-BRC-G-C-G [J].

KOPKA, ML ;

YOON, C ;

GOODSELL, D ;

PJURA, P ;

DICKERSON, RE .

JOURNAL OF MOLECULAR BIOLOGY, 1985, 183 (04) :553-563

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