Abstract:
:The binding kinetics of several benzimidazole compounds were determined with recombinant tubulin from benzimidazole-sensitive and -insensitive organisms. This study utilised the naturally occurring high efficacy of the benzimidazoles for the parasitic protozoa Giardia duodenalis and Encephalitozoon intestinalis, and low efficacy with Cryptosporidium parvum. Direct kinetic analysis of the benzimidazole-beta-tubulin interaction was performed using a fluorescence-based quenching method to determine the apparent association (k(on)) and dissociation (k(off)) rate constants from which the affinity constant (K(a)) was calculated. The binding kinetics were determined with recombinant alpha- and beta-tubulin from the parasitic protozoa with several benzimidazole R(2)-carbamate analogues. The affinity constant for the binding of several benzimidazoles with beta-tubulin from benzimidazole-sensitive protozoa was found to be significantly greater than binding to beta-tubulin from benzimidazole-insensitive protozoa. Additionally, the high affinity of several benzimidazole derivatives (albendazole, fenbendazole, mebendazole) for monomeric beta-tubulin and heterodimeric alphabeta-tubulin from benzimidazole-sensitive protozoa was also clearly demonstrated. The affinity constants determined with beta-tubulin from G. duodenalis and E. intestinalis also supported the observed in vitro efficacy of these compounds. The binding characteristics of the benzimidazoles with the highest in vitro efficacy (albendazole, fenbendazole, mebendazole) was reflected in their high association and slow dissociation rates with the beta-tubulin monomer or dimer from benzimidazole-sensitive protozoa compared with insensitive ones. Benzimidazole-bound alphabeta-tubulin heterodimers also had a significantly lower rate of microtubule assembly compared with benzimidazole-free alphabeta-heterodimers. The incorporation of benzimidazole-bound alphabeta-heterodimers into assembling microtubules was shown to arrest polymerisation in vitro although the addition of benzimidazole compounds to assembled microtubules did not result in depolymerisation. These findings indicate that a benzimidazole-beta-tubulin cap may be formed at the growing end of the microtubule and this cap prevents elongation of the microtubule.
journal_name
Mol Biochem Parasitoljournal_title
Molecular and biochemical parasitologyauthors
MacDonald LM,Armson A,Thompson AR,Reynoldson JAdoi
10.1016/j.molbiopara.2004.08.001subject
Has Abstractpub_date
2004-11-01 00:00:00pages
89-96issue
1eissn
0166-6851issn
1872-9428pii
S0166-6851(04)00214-2journal_volume
138pub_type
杂志文章abstract::Both patent and prepatent adult Hymenolepis diminuta excreted 20-hydroxyecdysone into the culture medium when maintained in vitro. Patent worms also excreted ecdysone and comparatively large quantities of unidentified immunoreactive material of a relatively apolar nature. This latter material was shown to be depleted ...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(87)90075-2
更新日期:1987-12-01 00:00:00
abstract::The variant surface glycoproteins (VSGs) of both metacyclic and bloodstream forms of Trypanosoma congolense are shown to be anchored to the plasma membrane through a glycolipid similar to that found in Trypanosoma brucei. Release of soluble VSG from both metacyclic and bloodstream forms is associated with the exposure...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(87)90045-4
更新日期:1987-01-15 00:00:00
abstract::cDNA clones encoding 473 amino acids of the knob-associated histidine-rich protein (PfHRPI) of Plasmodium falciparum clone FCR-3/A2 (Gambia) have been isolated and sequenced. Although a short region close to the amino terminus of the predicted sequence contains three blocks of six, seven or nine consecutive histidine ...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(87)90144-7
更新日期:1987-11-01 00:00:00
abstract::The capability of synthesizing fatty acids de novo in the meront stage of the oyster protozoan parasite, Perkinsus marinus, was investigated employing stable-isotope-labeled precursors (1,2 13C-acetate and palmitic-d(31) acid). Fatty acid methyl esters derived from 1,2 13C-acetate and palmitic-d(31) acid were analyzed...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/s0166-6851(01)00413-3
更新日期:2002-02-01 00:00:00
abstract::The emergence of drug-resistant Leishmania species is a significant problem in several countries. A comparative proteomic analysis of antimony-susceptible and antimony-resistant Leishmania braziliensis (LbSbR) and Leishmania infantum chagasi (LcSbR) lines was carried out using two-dimensional gel electrophoresis (2-DE...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2013.06.006
更新日期:2013-08-01 00:00:00
abstract::Giardia lamblia undergoes surface antigenic variation. The variant-specific surface proteins (VSPs) of isolate WB are cysteine-rich, can vary dramatically in size, contain Cys-X-X-Cys motifs, and are differentially expressed. GS/M(H7) is a Giardia clone from a different isolate which expresses a VSP epitope not found ...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(92)90072-r
更新日期:1992-04-01 00:00:00
abstract::Cathepsin B-like cysteine protease (cbl) genes produce the most abundant mRNAs ( approximately 16%) detected in the adult female intestine of the parasitic nematode Haemonchus contortus. CBL enzymes appear to digest host proteins and are vaccine candidates for immune control of H. contortus and potentially other paras...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2004.06.010
更新日期:2004-10-01 00:00:00
abstract::Plasmodium falciparum merozoites invade erythrocytes using a range of alternative ligands that includes erythrocyte binding antigenic proteins (EBAs) and reticulocyte binding protein homologues (Rh). Variation in the expression of some of these genes among culture-adapted parasite lines correlates with the use of diff...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2006.05.014
更新日期:2006-10-01 00:00:00
abstract::In trypanosomes, trans-splicing is a major essential RNA-processing mechanism that involves the addition of a spliced leader sequence to all mRNAs from a small RNA species, known as the spliced leader RNA (SL RNA). SL RNA maturation is poorly understood and it is not clear where assembly with Sm proteins takes place. ...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2006.07.004
更新日期:2006-12-01 00:00:00
abstract::Two proteins were previously described in the excretory-secretory products (ES) collected from Dirofilaria immitis during the molt from the third stage to the fourth stage in vitro. The two proteins were purified using cation exchange and reverse phase HPLC. During the purification of these two proteins, a third prote...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(95)02533-2
更新日期:1996-01-01 00:00:00
abstract::Adults of Onchocerca volvulus and Onchocerca gibsoni were identically fractionated into a surface-enriched fraction, a phosphate buffered saline (PBS) extract and a PBS insoluble-detergent soluble fraction. Glycoproteins were prepared from these extracts and all fractions were examined by the Western blot technique us...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(86)90102-7
更新日期:1986-09-01 00:00:00
abstract::The extent of structural conservation of the Plasmodium falciparum sporozoite surface protein gene, STARP, recently characterized in the T9/96 clone, has been analyzed using the polymerase chain reaction. Results from Ivory Coast and Thai clones, field isolates originating from Brazil and Kenya and laboratory-maintain...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(94)00138-3
更新日期:1994-10-01 00:00:00
abstract::In most organisms rDNA transcription ceases under conditions of growth stress. However, we have earlier shown that pre-rRNA accumulates during encystation in Entamoeba invadens. We labeled newly-synthesized rRNA during encystation, with [methyl-(3)H] methionine in the presence of chitinase to enable uptake of isotope....
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2014.05.003
更新日期:2014-06-01 00:00:00
abstract::Replication of kinetoplast DNA minicircles in Crithidia fasciculata occurs by a unidirectional mechanism involving continuous synthesis of one strand (L strand) and discontinuous synthesis of the complementary strand (H strand). L-strands are initiated by RNA priming at alternate origins (A and B) resulting in daughte...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/s0166-6851(01)00272-9
更新日期:2001-06-01 00:00:00
abstract::Steroids and retinoids are important regulators of development in invertebrates and vertebrates. The central mediators of action of these compounds are their cognate receptors, which together form a family of proteins known as the nuclear receptor family. Previous studies have demonstrated that the genome of Onchocerc...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/s0166-6851(99)00152-8
更新日期:1999-11-30 00:00:00
abstract::Parasitic infections are a widespread health problem and research of novel anthelmintic compounds is of the utmost importance. In this study we performed a virtual screening campaign by coupling ligand-based pharmacophore, homology modeling and molecular docking. The virtual screening campaign was conducted using a jo...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2021.111350
更新日期:2021-01-07 00:00:00
abstract::Hamsters infected with Opisthorchis viverrini, a liver fluke of man, showed an increased deposition of collagen in their livers. However, increased collagen breakdown as well as its synthesis were observed in the infected livers. Thus, stimulated synthesis might be the main factor responsible for the net increase in c...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(83)90035-x
更新日期:1983-05-01 00:00:00
abstract::Protozoan parasites of the genus Leishmania have a digenetic lifecycle, alternating between the promastigote and amastigote stages. The extracellular promastigote resides within a sandfly vector, while the obligate intracellular amastigote stage replicates in the phagolysosome of mammalian host macrophages. Adaptation...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2007.02.010
更新日期:2007-06-01 00:00:00
abstract::Recent advances in insect genetic engineering have opened up new possibilities in the genetic control of insect vectors of human diseases. We outline the current state of the sterile insect technique and show how the use of engineered dominant lethals can greatly increase the effectiveness of this approach. We conside...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章,评审
doi:10.1016/s0166-6851(02)00040-3
更新日期:2002-05-01 00:00:00
abstract::Glycosomes are peroxisome-like organelles present in trypanosomatid pathogens. These organelles compartmentalize glycolysis, among other reactions, and are essential in both bloodstream and procyclic form Trypanosoma brucei. Peroxins (PEXs) are proteins necessary for biogenesis of peroxisomes and glycosomes. In each a...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2005.03.008
更新日期:2005-07-01 00:00:00
abstract::Heartworm disease caused by Dirofilaria immitis affects canine and feline hosts. Moreover, the parasite can infect humans, causing pulmonary dirofilariosis. Most affected dogs have patent infections with circulating microfilariae in peripheral blood, although infected dogs sometimes develop occult infections character...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2009.03.005
更新日期:2009-08-01 00:00:00
abstract::A novel Plasmodium falciparum sporozoite antigen, STARP (Sporozoite Threonine and Asparagine-Rich Protein), detected consistently on the surface of sporozoites obtained from laboratory strains and field isolates, has been identified and cloned, following a systematic approach aimed at isolating novel non-CS sporozoite...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(94)00012-3
更新日期:1994-04-01 00:00:00
abstract::Cryptosporidium parvum is a protozoan parasite which produces self-limited disease in immunocompetent hosts and devastating, persistent diarrhea in immunocompromised individuals. There is no effective treatment for cryptosporidiosis and little is known about the basic biology of the organism. Cloning and sequence anal...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/s0166-6851(98)00119-4
更新日期:1998-10-30 00:00:00
abstract::We have successfully transfected Entamoeba histolytica trophozoites with constructs containing ferredoxin sequences fused to the reporter gene luciferase. We have determined the conditions and parameters necessary to maximise transient luciferase expression in our system. Our optimal construct gave values of 268 x 10(...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(95)02474-3
更新日期:1995-10-01 00:00:00
abstract::Trypanosoma cruzi presents high genetic diversity and parasite isolates show remarkable differences in biological parameters. In this study, we evaluated whether DNA microarrays containing CL Brener cDNAs can be used for comparative genomics and for the analysis of gene expression in T. cruzi. We constructed a prototy...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2004.06.017
更新日期:2004-12-01 00:00:00
abstract::Purified GP57/51, a Trypanosoma cruzi glycoprotein earlier identified as a major antigen in infected humans, was subjected to N-terminal sequence analysis. Alignment of the first 30 amino acids revealed that its N-terminal region is virtually identical to that reported for a cysteine-proteinase isolated from the Tulah...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(90)90127-8
更新日期:1990-11-01 00:00:00
abstract::A Fasciola hepatica cDNA clone of 1752 bp was isolated from an adult worm cDNA expression library by immunological screening using a rabbit serum against the excretory-secretory antigens. The nucleotide sequence of the cDNA revealed the presence of an open reading frame of 489 codons which encoded a 55 kDa polypeptide...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/s0166-6851(02)00269-4
更新日期:2003-01-01 00:00:00
abstract::The origin of membraneous structures in the cytoplasm of human erythrocytes infected with the malaria parasite, Plasmodium falciparum, was determined by confocal fluorescence imaging microscopy. When infectious merozoites invaded erythrocytes labeled with the fluorescent, lipophilic, non-exchangeable molecules DiIC16 ...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/0166-6851(94)90038-8
更新日期:1994-07-01 00:00:00
abstract::Conserved amongst all eukaryotes is a family of mitochondrial carrier proteins (SLC25A) responsible for the import of various solutes across the inner mitochondrial membrane. We previously reported that the human parasite Trypanosoma brucei possesses 26 SLC25A proteins (TbMCPs) amongst which two, TbMCP11 and TbMCP8, w...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2020.111275
更新日期:2020-05-01 00:00:00
abstract::Glutamate-cysteine ligase (GCL) is a heterodimer enzyme composed of a catalytic subunit (GCLC) and a modifier subunit (GCLM). This enzyme catalyses the synthesis of γ-glutamylcysteine, a precursor of glutathione. cDNAs of the putative glutamate-cysteine ligase catalytic (Ace-GCLC) and modifier subunits (Ace-GCLM) of A...
journal_title:Molecular and biochemical parasitology
pub_type: 杂志文章
doi:10.1016/j.molbiopara.2014.07.003
更新日期:2014-08-01 00:00:00