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2.
J Drug Deliv ; 2018: 2851579, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30534433

RESUMO

Cationic liposomes with DNA-transportation properties have attracted considerable attention for their ability to deliver medicinal oligonucleotides to mammalian cells. Amongst these are metalloliposomes that use transition metal ions to confer the lipid molecules cationic charge and unique advantages such as redox- and ligand-exchange triggered DNA-release properties. In this study, lipophilic copper (II) and zinc (II) complexes of 1-alkyl-1,4,7-triazacyclononane were prepared to investigate their ability to bind and transfect double stranded DNA with mammalian cells in vitro and in vivo. The copper(II)-surfactant complexes Cu(TACN-C8)2 (1), Cu(TACN-C10)2 (2), Cu(TACN-C12)2 (3), Cu(TACN-C14)2 (4), Cu(TACN-C16)2 (5), and Cu(TACN-C18)2 (6) that comprise ligands that vary in the length of the alkyl group and the zinc (II)-surfactant complex of Zn(TACN-C12)2 (7) were synthesized. The critical micelle concentration (CMC) for 1-7 was measured using fluorescence spectroscopy and an evaluation of the transfection efficiency of the complexes was assessed using the pEGFP-N1 plasmid and HEK 293-T cells. An inverse relationship between DNA transfection efficiency and CMC of the Cu(II) metallosurfactants was observed. The highest transfection efficiency of 38% was observed for Cu(TACN-C12)2 corresponding to the surfactant with dodecyl alkyl chain having a CMC of 50 µM. Further, an in vivo experiment using mice models was conducted to test the Cu(TACN-C12)2 (3) and Zn(TACN-C12)2 (7) metallosurfactants delivering a DNA vaccine designed for protection against leishmaniasis disease and the study revealed that the Cu-lipoplex elicited the production of significantly more T cells than the Zn-lipoplex and the control group in vivo.

3.
Chembiochem ; 16(13): 1884-1889, 2015 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-26227417

RESUMO

Low yields and substantial epimerization of peptide-α-thioesters often compromise the overall efficiency of native chemical ligation (NCL). Peptide arylthioesters are more reactive than peptide alkylthioesters in NCL, but are also more difficult to handle due to their propensity to hydrolyze, and are therefore often generated in situ. However, pre-prepared peptide arylthioesters are required for some NCL applications. Here we present a 7-nitroindoline-based photochemical method that generates protected peptide phenylthioesters under neutral reaction conditions via their activated esters from photoreactive peptide precursors in high isolated yields, and with low levels of epimerization. This method is fully compatible with Fmoc-strategy solid-phase peptide synthesis. Global deprotection with trifluoroacetic acid furnishes peptide phenylthioesters for NCL. Photoreactive peptide precursors can also be converted into their hydrazides in two steps by this method.

4.
Artigo em Inglês | MEDLINE | ID: mdl-25710357

RESUMO

An efficient overall two-step strategy for the synthesis of (E)-5-aminoallyl-pyrimidine-5'-triphoshate, starting from commercially available pyrimidine-5'-triphosphate is described. The method involves regioselective iodination of pyrimidine-5'-triphosphate, followed by the palladium-catalyzed Heck coupling with allylamine. The catalytic reaction is highly stereoselective and compatible with many functional groups present in the reactants.


Assuntos
Paládio/química , Polifosfatos/química , Polifosfatos/síntese química , Pirimidinas/química , Catálise , Técnicas de Química Sintética , Estereoisomerismo
5.
Org Biomol Chem ; 11(34): 5579-83, 2013 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-23863943

RESUMO

A synthetic glycoarray containing non-reducing α-galactopyranosyl moieties related to mucin O-glycans of the parasite Trypanosoma cruzi was evaluated by a chemiluminescent enzyme-linked immunosorbent assay with sera from patients with chronic Chagas disease. Our data revealed the disaccharide Galα(1,3)Galß as the immunodominant glycotope, which may eventually be employed as a diagnostic antigen for Chagas disease.


Assuntos
Doença de Chagas/diagnóstico , Epitopos/química , Galactose/química , Trypanosoma cruzi/química , Reações Antígeno-Anticorpo , Configuração de Carboidratos , Doença de Chagas/imunologia , Doença de Chagas/microbiologia , Ensaio de Imunoadsorção Enzimática , Epitopos/imunologia , Galactose/imunologia , Humanos , Trypanosoma cruzi/imunologia
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