RESUMEN
The development of multifunctional vectors for efficient and safe gene delivery is one of the major challenges for scientists working in the gene therapy field. In this context, we have designed a novel type of aminoglycoside-rich dendrimers with a defined structure based on polyamidoamine (PAMAM) in order to develop efficient, nontoxic gene delivery vehicles. Three different conjugates, i.e., PAMAM G4-neamine, -paromomycin, and -neomycin, were synthesized and characterized by nuclear magnetic resonance (NMR) and MALDI analysis. The conjugates were found to self-assemble electrostatically with plasmid DNA, and unlike neamine conjugate, each at its optimum showed increased gene delivery potency compared to PAMAM G4 dendrimer in three different cell lines, along with negligible cytotoxicity. These results all disclosed aminoglycosides as suitable functionalities for tailoring safe and efficient multifunctional gene delivery vectors.
Asunto(s)
Aminoglicósidos/química , Dendrímeros/química , Vectores Genéticos/química , Vectores Genéticos/genética , Nylons/química , Transfección/métodos , Animales , Células COS , Chlorocebus aethiops , Células HeLa , Humanos , Conformación Molecular , Plásmidos/química , Plásmidos/genética , Células Tumorales CultivadasRESUMEN
The development of new methods for linking sugars to heterocycles and peptides is an attractive area of research because glyco-conjugates play important roles in biology and medicine and are indispensable tools for probing several processes. Herein we report a one-pot, three-component sequential procedure for the synthesis of a novel class of glyco-conjugates, i.e. glyco-hydantoin conjugates, in high yields and very mild conditions, using readily accessible starting materials. We also demonstrated that some of the glyco-hydantoin conjugates obtained are synthons for the preparation of a novel class of glyco-pseudopeptides in which the amino acid is tethered to the sugar through the hydantoin ring.
Asunto(s)
Carbohidratos/química , Glicoconjugados/síntesis química , Hidantoínas/química , Glicoconjugados/química , Estructura MolecularRESUMEN
We report a new and fast domino synthesis of aminoalcohols under mild conditions. The free-radical reaction of aliphatic and aromatic amines with alcohol cosolvents is promoted by means of the TiCl(4)-Zn/t-BuOOH system. According to the proposed mechanism, the amine reacts with two molecules of alcohol in an electrophilic-nucleophilic cascade process. This procedure, if compared with the TiCl(3)/t-BuOOH-mediated protocol previously reported, appears to be more selective, of more general applicability and affords the desired products in higher yields. Besides, with the same catalytic system it was possible to promote the reaction of primary arylamines with two molecules of cyclic ether, leading to the formation of a wider range of functionalized aminoalcohols.
Asunto(s)
Alcoholes/síntesis química , Aminas/química , Éteres Cíclicos/química , Solventes/química , Titanio/química , Zinc/química , terc-Butilhidroperóxido/química , Alcoholes/química , Alquilación , Radicales Libres/química , Especificidad por SustratoRESUMEN
An amine, an aldehyde, and methanol can be readily assembled in one pot under very mild conditions through a free-radical multicomponent reaction by using an aqueous acidic TiCl3/t-BuOOH system to afford 1,2-amino alcohols in fair to excellent yields.