Inhibition of Enzyme Activity of Rhipicephalus (Boophilus) microplus Triosephosphate Isomerase and BME26 Cell Growth by Monoclonal Antibodies

Saramago, Luiz; Franceschi, Mariana F. S.; Logullo, Carlos; Masuda, Aoi; Vaz, Itabajara da Silva; Farias, Sandra Estrazulas; Moraes, João Antônio de

doi:10.3390/ijms131013118

Cited by 9 publications

(10 citation statements)

References 66 publications

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“…This approach has also been adopted in other parasites. Monoclonal antibodies raised against TPI have been shown to reduce the growth of the protozoan Trypanosoma cruzi , the tick Rhipicephalus ( Boophilus ) microplus and the tapeworm Taenia solium [31–33]. This strengthens the argument that TPI is a potential vaccine target in a variety of pathogens.…”

Section: Introductionsupporting

confidence: 55%

Triose phosphate isomerase from the blood fluke Schistosoma mansoni: Biochemical characterisation of a potential drug and vaccine target

Zinsser¹,

Farnell²,

Dunne³

et al. 2013

FEBS Letters

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a b s t r a c tThe glycolytic enzyme triose phosphate isomerase from Schistosoma mansoni is a potential target for drugs and vaccines. Molecular modelling of the enzyme predicted that a Ser-Ala-Asp motif which is believed to be a helminth-specific epitope is exposed. The enzyme is dimeric (as judged by gel filtration and cross-linking), resistant to proteolysis and highly stable to thermal denaturation (melting temperature of 82.0°C). The steady-state kinetic parameters are high (K m for dihydroxyacetone phosphate is 0.51 mM; K m for glyceraldehyde 3-phosphate is 1.1 mM; k cat for dihydroxyacetone phosphate is 7800 s À1 and k cat for glyceraldehyde 3-phosphate is 6.9 s À1). Structured summary of protein interactions:SmTPI and SmTPI bind by cross-linking study (View interaction) SmTPI and SmTPI bind by molecular sieving (View interaction)

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Section: Introductionsupporting

confidence: 55%

Triose phosphate isomerase from the blood fluke Schistosoma mansoni: Biochemical characterisation of a potential drug and vaccine target

Zinsser¹,

Farnell²,

Dunne³

et al. 2013

FEBS Letters

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“…(B.) microplus triosephosphate isomerase (TIM), an fundamental enzyme in the energy metabolism during embryogenesis was be inhibited by antibodies (SARAMAGO et al, 2012) and by sulfhydryl reagents that interfere in essential cysteine residues of the BmTIM (MORAES et al, 2011). Also, a catalase inhibitor (3-amino-1,2,4-triazole) induced deleterious effects to R.…”

Section: Embryo Proteins As Targets For Tick Controlmentioning

confidence: 99%

The dynamics of energy metabolism in the tick embryo

Martins

Ruiz

Fonseca

et al. 2018

Rev. Bras. Parasitol. Vet.

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The cattle tick Rhipicephalus (Boophilus) microplus is an ectoparasite capable of transmitting a large number of pathogens, causing considerable losses in the cattle industry, with substantial damage to livestock. Over the years, important stages of its life cycle, such as the embryo, have been largely ignored by researchers. Tick embryogenesis has been typically described as an energy-consuming process, sustaining cell proliferation, differentiation, and growth. During the embryonic stage of arthropods, there is mobilization of metabolites of maternal origin for the development of organs and tissues of the embryo. Glycogen resynthesis in late embryogenesis is considered as an effective indicator of embryonic integrity. In the cattle tick R.(B. (B.) microplus, glycogen resynthesis is sustained by protein degradation through the gluconeogenesis pathway at the end of the embryonic period. Despite recent advancements in research on tick energy metabolism at the molecular level, the dynamics of nutrient utilization during R. (B.) microplus embryogenesis is still poorly understood. The present review aims to describe the regulatory mechanisms of carbohydrate metabolism during maternal-zygotic transition and identify possible new targets for the development of novel drugs and other control measures against R. (B.) microplus infestations.

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“…One example is the observation that RNAi silencing of AamAV422, an Amblyomma americanum salivary gland protein, reduces the tick blood meal [ 12 ]. Another example is the demonstration that monoclonal antibodies against triosephosphate isomerase (TIM) can inhibit its enzymatic activity and cellular proliferation of the embryonic tick cell line (BME26) [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Novel and Selective Rhipicephalus microplus Triosephosphate Isomerase Inhibitors with Acaricidal Activity

Saramago

Gomes

Aguilera

et al. 2018

Veterinary Sciences

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The cattle tick Rhipicephalus microplus is one of the most important ectoparasites causing significant economic losses for the cattle industry. The major tool of control is reducing the number of ticks, applying acaricides in cattle. However, overuse has led to selection of resistant populations of R. microplus to most of these products, some even to more than one active principle. Thus, exploration for new molecules with acaricidal activity in R. microplus has become necessary. Triosephosphate isomerase (TIM) is an essential enzyme in R. microplus metabolism and could be an interesting target for the development of new methods for tick control. In this work, we screened 227 compounds, from our in-house chemo-library, against TIM from R. microplus. Four compounds (50, 98, 14, and 161) selectively inhibited this enzyme with IC50 values between 25 and 50 μM. They were also able to diminish cellular viability of BME26 embryonic cells by more than 50% at 50 μM. A molecular docking study showed that the compounds bind in different regions of the protein; compound 14 interacts with the dimer interface. Furthermore, compound 14 affected the survival of partially engorged females, fed artificially, using the capillary technique. This molecule is simple, easy to produce, and important biological data—including toxicological information—are available for it. Our results imply a promising role for compound 14 as a prototype for development of a new acaricidal involving selective TIM inhibition.

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Inhibition of Enzyme Activity of Rhipicephalus (Boophilus) microplus Triosephosphate Isomerase and BME26 Cell Growth by Monoclonal Antibodies

Cited by 9 publications

References 66 publications

Triose phosphate isomerase from the blood fluke Schistosoma mansoni: Biochemical characterisation of a potential drug and vaccine target

Triose phosphate isomerase from the blood fluke Schistosoma mansoni: Biochemical characterisation of a potential drug and vaccine target

The dynamics of energy metabolism in the tick embryo

Novel and Selective Rhipicephalus microplus Triosephosphate Isomerase Inhibitors with Acaricidal Activity

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