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1.
Eur J Med Chem ; 180: 143-153, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31302447

RESUMO

The rise of antibiotic resistance has necessitated the development of alternative strategies for the treatment of infectious diseases. Antimicrobial peptides (AMPs), components of the innate immune response in various organisms, are promising next-generation drugs against bacterial infections. The ability of the medicinal leech Hirudo medicinalis to store blood for months with little change has attracted interest regarding the identification of novel AMPs in this organism. In this study, we employed computational algorithms to the medicinal leech genome assembly to identify amino acid sequences encoding potential AMPs. Then, we synthesized twelve candidate AMPs identified by the algorithms, determined their secondary structures, measured minimal inhibitory concentrations against three bacterial species (Escherichia coli, Bacillus subtilis, and Chlamydia thrachomatis), and assayed cytotoxic and haemolytic activities. Eight of twelve candidate AMPs possessed antimicrobial activity, and only two of them, 3967 (FRIMRILRVLKL) and 536-1 (RWRLVCFLCRRKKV), exhibited inhibition of growth of all tested bacterial species at a minimal inhibitory concentration of 10 µmol. Thus, we evidence the utility of the developed computational algorithms for the identification of AMPs with low toxicity and haemolytic activity in the medicinal leech genome assembly.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Farmacorresistência Bacteriana/efeitos dos fármacos , Algoritmos , Animais , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/química , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/crescimento & desenvolvimento , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Chlamydia/efeitos dos fármacos , Chlamydia/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Hirudo medicinalis , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
2.
Nanoscale Res Lett ; 12(1): 87, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28168611

RESUMO

Here we report on the analysis of the effect of the doping of CdP2 single crystals by ZnP2 nanoclusters on the dispersion of the surface polaritons (SP). The ATR spectroscopic technique has been applied to excite the SP in the CdXZn(1-X)P2 system. Analysis of the obtained spectra has shown that the doping of CdP2 single crystals by ZnP2 nanoclusters result in the position and the width of the dispersion branches of the SP. This effect is more pronounced in the low frequency dispersion branches. These SP branches are originated from phonons which correspond to the motion of the cation sublattice.

3.
J Inorg Biochem ; 79(1-4): 41-6, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10830845

RESUMO

In order to mimic dinuclear active sites of some non-heme diiron proteins, ten new polydentate and potentially dinucleating ligands have been synthesized. Each ligand contains a carboxylate moiety designed to bridge two metal atoms. These central carboxylate moieties are derived from substituted benzoic acids that in turn are linked to terminal nitrogen or oxygen donors by spacers so that framework-type polydentate ligands similar to the polypeptide frames in diiron metallobiosites are formed. Reaction of these ligands with Fe(ClO4)3 x 9H2O leads to ferric mu-oxo-mu-carboxylato iron complexes of the general formulas [Fe2O(L)2(H2O)2](ClO4)2 and [Fe2O(L)(BzO)](ClO4)2 (L = ligand), containing one or two immobilized bridging carboxylates, respectively. While X-ray crystallography shows that some of these complexes are dimers or network polymers in the solid state, electrospray ionization mass spectrometry (ESMS) and spectroscopic data (UV-Vis, NMR, Móssbauer) indicate that they dissociate to monomeric Fe2O units in dilute CH3CN solutions.


Assuntos
Ácidos Carboxílicos/química , Ferro/química , Ferro/metabolismo , Metaloproteínas/química , Metaloproteínas/metabolismo , Sítios de Ligação , Ácidos Carboxílicos/metabolismo , Cristalografia por Raios X , Desenho de Fármacos , Ligantes , Espectrometria de Massas , Modelos Moleculares , Conformação Molecular
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