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1.
Toxicon ; 184: 143-151, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32522618

RESUMO

Toxopneustes roseus is a species of sea urchin with a wide distribution along the eastern Pacific coast. It belongs to the Toxopneustidae family and, like its members, has well-developed globiferous pedicellariae that exert a variety of pharmacological actions. We identified six volatile non-peptide molecules from its globiferous pedicellariae by using GC-MS and RP-HPLC-MS/MS, including: benzoic acid; 2-aminoethanol (MEA); 2-(dimethylamine) ethanol (DMAE); 1- (4-bromophenyl)-1-phenylethanol (BPPE); 2-[1-(4-bromophenyl)-1- phenylethoxy]-N,N-dimethylethanamine (EMB); and 2-[1-(4-chlorphenyl)-1- phenylethoxy]-N,N-dimethylethanamine (CLX). The construction of a pharmacophore model and the in silico molecular docking of EMB and CLX into the human voltage-gated sodium channel hNaV1.7 allowed establishing that these molecules are structurally similar to local anesthetics and other NaV channel blockers and can bind to the same site receptor in NaV channels; suggesting that both molecules are active components in T. roseus venom. Furthermore, a viable endogenous biopathway is proposed in which T. roseus can synthesize EMB and CLX from benzoic acid, MEA, DMAE, and BPPE as their precursors, which would emphasize the importance of these molecules in the metabolism of this sea urchin.


Assuntos
Ouriços-do-Mar , Peçonhas , Sequência de Aminoácidos , Animais , Sítios de Ligação , Humanos , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem
2.
Pestic Biochem Physiol ; 145: 56-65, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29482732

RESUMO

Tomato yellow leaf curl virus (TYLCV; genus Begomovirus; family Geminiviridae) infects mainly plants of the family Solanaceae, and the infection induces curling and chlorosis of leaves, dwarfing of the whole plant, and reduced fruit production. Alternatives for direct control of TYLCV and other geminiviruses have been reported, for example, the use of esterified whey proteins, peptide aptamer libraries or artificial zinc finger proteins. The two latter alternatives affect directly the replication of TYLCV as well as of other geminiviruses because the replication structures and sequences are highly conserved within this virus family. Because peptides and proteins offer a potential solution for virus replication control, in this study we show the isolation, biochemical characterization and antiviral activity of a peptide derived from globulins of amaranth seeds (Amaranthus hypochondriacus) that binds to the replication origin sequence (OriRep) of TYLCV and affects viral replication with a consequent reduction of disease symptoms in Nicotiana benthamiana. Aromatic peptides obtained from papain digests of extracted globulins and albumins of amaranth were tested by intrinsic fluorescent titration and localized surface resonance plasmon to analyze their binding affinity to OriRep of TYLCV. The peptide AmPep1 (molecular weight 2.076 KDa) showed the highest affinity value (Kd = 1.8 nM) for OriRep. This peptide shares a high amino acid similarity with a part of an amaranth 11S globulin, and the strong affinity of AmPep1 could be explained by the presence of tryptophan and lysine facilitating interaction with the secondary structure of OriRep. In order to evaluate the effect of the peptide on in vitro DNA synthesis, rolling circle amplification (RCA) was performed using as template DNA from plants infected with TYLCV or another begomovirus, pepper huasteco yellow vein virus (PHYVV), and adding AmPep1 peptide at different concentrations. The results showed a decrease in DNA synthesis of both viruses at increasing concentrations of AmPep1. To further confirm the antiviral activity of the peptide in vivo, AmPep1 was infiltrated into leaves of N. benthamiana plants previously infected with TYLCV. Plants treated with AmPep1 showed a significant decrease in virus titer compared with untreated N. benthamiana plants as well as reduced symptom progression due to the effect of AmPep1 curtailing TYLCV replication in the plant. The peptide also showed antiviral activity in plants infected with PHYVV. This is the first report, in which a peptide is directly used for DNA virus control in plants, supplied as exogenous application and without generation of transgenic lines.


Assuntos
Amaranthus/metabolismo , Begomovirus/genética , Globulinas/metabolismo , Nicotiana/virologia , Peptídeos/metabolismo , Origem de Replicação , Replicação Viral , Antivirais/farmacologia , Begomovirus/efeitos dos fármacos , Begomovirus/isolamento & purificação , Begomovirus/fisiologia , Sítios de Ligação , Produtos Agrícolas/efeitos dos fármacos , Produtos Agrícolas/virologia , Peptídeos/isolamento & purificação , Peptídeos/farmacologia , Extratos Vegetais/metabolismo , Nicotiana/efeitos dos fármacos , Carga Viral/efeitos dos fármacos
3.
Curr Med Chem ; 11(12): 1657-69, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15180570

RESUMO

Selenium is an essential trace element. It is, however toxic at concentration little above which is required for health. Selenium is incorporated into proteins as selenocysteine, the 21(st) amino acid. Selenoproteins are found in bacteria, archaea and eukaryotes. Biochemical and physicochemical properties of selenium result in the unique redox characteristics of selenocysteine and its use in antioxidant enzymes. In this context of a redox reaction is the reduction of reactive oxygen metabolites by glutathione peroxidases, helping to maintain membrane integrity, reduces the oxidative damage to lipids, lipoproteins, and DNA. Selenium has structural and enzymatic roles. Selenium influences a number of endocrine processes, most notably, those involved in thyroid hormone synthesis and metabolism. Se is needed for the proper functioning of the immune system, a role in viral suppression, AIDS, and also is implicated in delaying the aging process. Its deficiency has been linked to a number of disorders such as heart disease, diabetes, and diseases of the liver, and it is required for sperm motility and may reduce the risk of miscarriage. Se supplementation has recently moved from the realm of correcting nutritional deficiencies to one of pharmacological intervention, especially in the clinical domain of cancer chemoprevention. During the last few years, a tremendous effort has been directed toward the synthesis of stable organoselenium compounds that could be used as antioxidants, enzyme modulators, antitumor, antimicrobials, antihypertensive agents, antivirals and cytokine inducers. The biochemistry and pharmacology of selenium-based compounds are subjects of intense current interest, especially from the point of view of public heath. The purpose of this review is to discuss the recent pharmacological applications of organoselenium compounds as therapeutic agents in the treatment of several diseases.


Assuntos
Compostos Organosselênicos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Anticarcinógenos/química , Anticarcinógenos/farmacologia , Anticarcinógenos/uso terapêutico , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Humanos , Modelos Biológicos , Compostos Organosselênicos/química , Compostos Organosselênicos/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Relação Estrutura-Atividade
5.
Acta Crystallogr D Biol Crystallogr ; 55(Pt 2): 577-80, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10089385

RESUMO

In attempts to obtain protein crystals of a sufficient size for structural studies, lack of knowledge of the physicochemical properties of protein solutions and of their crystal-growth behaviour lead to a bottleneck for drug design as well as for X-ray crystallography. Most formal investigations on crystal-growth phenomena have been focused on equilibrium studies, where the protein is soluble, and on the kinetics of crystal growth, which is related to both nucleation and crystal-growth phenomena. The aim of this work is to measure the crystal-growth rate along a capillary tube used as a growing cell. These experiments were carried out using the gel-acupuncture technique [García-Ruiz et al. (1993). Mater. Res. Bull. 28, 541-546; García-Ruiz & Moreno (1994). Acta Cryst. D50, 484-490; García-Ruiz & Moreno (1997). J. Cryst. Growth, 178, 393-401]. Crystal-growth investigations took place using lysozyme and thaumatin I as standard proteins. The maximum average growth rate obtained in the lower part of the capillary tube was about 35 A s-1 and the minimum average growing rate in the upper part of the capillary tube was about 8 A s-1. The crystal-growth rate as a function of the supersaturation was experimentally estimated at a constant height along the capillary tube.


Assuntos
Proteínas/química , Precipitação Química , Cristalização , Cinética , Proteínas/isolamento & purificação
6.
Biochim Biophys Acta ; 1384(1): 7-15, 1998 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-9602025

RESUMO

Based on circular dichroism (CD), we have found an essential (i, i + 4) alpha-helix stabilizing array in the C-terminus region for the cholesteryl ester transfer protein (CETP) between histidine 466 and aspartic acid 470. This region apparently corresponds to an amphipathic alpha-helix. The behavior of this peptide in solution in comparison with a mutant peptide (D470N) was also analyzed by dynamic light scattering (DLS). The results showed that alpha-helix stabilization is not due to peptide aggregation. The thermodynamic estimation of stability supports the idea that the phenomenon is carried out through an (i, i + 4) array. The representation of the C-terminal region as an amphipathic alpha-helical peptide shows that lipid-binding activity might be in part due to both the asymmetric polar/non-polar residue distribution and to the presence of an (i, i + 4) array important for helix stability.


Assuntos
Proteínas de Transporte/química , Glicoproteínas , Fragmentos de Peptídeos/química , Dobramento de Proteína , Sequência de Aminoácidos , Proteínas de Transporte/genética , Proteínas de Transferência de Ésteres de Colesterol , Dicroísmo Circular , Dados de Sequência Molecular , Mutação , Fragmentos de Peptídeos/genética , Relação Estrutura-Atividade
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