Novel dehydropeptide-based magnetogels containing manganese ferrite nanoparticles as antitumor drug nanocarriers.

Herein, novel dehydropeptide-based magnetogels, based on the hydrogelators Npx-l-Phe-Z-ΔAbu-OH, Npx-l-Trp-Z-ΔPhe-OH and Npx-l-Ala-Z-ΔPhe-Gly-l-Arg-Gly-l-Asp-Gly-OH and containing manganese ferrite nanoparticles (diameters around 20 nm), were prepared and characterized. TEM and FTIR measurements showed that the magnetogels maintained the fibrous structure of neat hydrogels, with fibres of ca. 20 nm average width (generally in the range 10-30 nm) and a few conformational changes relative to the neat hydrogels. The magnetogels were tested as nanocarriers for two potential fluorescent antitumor drugs: a thienopyridine derivative and the natural compound curcumin. FRET (Förster resonance energy transfer) from the aromatic moieties (energy donors) of gels to the fluorescent drugs (energy acceptors) and fluorescence anisotropy measurements confirmed the incorporation of both drugs into the magnetogel matrices. The transport of both drugs loaded into the magnetogels to membrane models (small unilamellar vesicles) was assessed by FRET between the fluorescent drugs and the dye Nile Red. The magnetogel possessing the RGD sequence was most promising for the delivery of the thienopyridine derivative, whereas three magnetogels were found to be suitable for the delivery of curcumin.

New self-assembled supramolecular hydrogels based on dehydropeptides.

Supramolecular hydrogels rely on small molecules that self-assemble in water as a result of the cooperative effect of several relatively weak intermolecular interactions. Peptide-based low molecular weight hydrogelators have attracted enormous interest owing to the simplicity of small molecules combined with the versatility and biocompatibility of peptides. In this work, naproxen, a well known non-steroidal anti-inflammatory drug, was N-conjugated with various dehydrodipeptides to give aromatic peptide amphiphiles that resist proteolysis. Molecular dynamics simulations were used to obtain insight into the underlying molecular mechanism of self-assembly and to rationalize the design of this type of hydrogelators. The results obtained were in excellent agreement with the experimental observations. Only dehydrodipeptides having at least one aromatic amino acid gave hydrogels. The characterization of the hydrogels was carried out using transmission electron microscopy (TEM), circular dichroism (CD), fluorescence spectroscopy and also rheological assays.

Synthesis of new ß-amidodehydroaminobutyric acid derivatives and of new tyrosine derivatives using copper catalyzed C-N and C-O coupling reactions.

Several ß-amidodehydroaminobutyric acid derivatives were prepared from N,C-diprotected ß-bromodehydroaminobutyric acids and amides by a copper catalyzed C-N coupling reaction. The best reaction conditions include the use of a catalytic amount of CuI, N,N'-dimethylethylenediamine as ligand and K(2)CO(3) as base in toluene at 110 °C. The stereochemistry of the products was determined using NOE difference experiments and the results obtained are in agreement with an E-stereochemistry. Thus, the stereochemistry is maintained in the case of the E-isomers of ß-bromodehydroaminobutyric acid derivatives, but when the Z-isomers were used as substrates the reaction proceeds with inversion of configuration. The use of ß-bromodehydrodipeptides as substrates was also tested. It was found that the reaction outcome depend on the stereochemistry of the ß-bromodehydrodipeptide and on the nature of the first amino acid residue. The products isolated were the ß-amidodehydrodipeptide derivatives and/or the corresponding dihydropyrazines. The same catalytic system (CuI/N,N'-dimethylethylene diamine) was used in the C-O coupling reactions between a tyrosine derivative and aryl bromides. The new O-aryltyrosine derivatives were isolated in moderate to good yields. The photophysical properties of two of these compounds were studied in four solvents of different polarity. The results show that these compounds after deprotection can be used as fluorescence markers.

Treatment of morbid obesity with adjustable gastric band: preliminary report.

BACKGROUND: The goal of surgery for morbid obesity is to achieve a good and durable loss of weight and improve health. Previous studies have demonstrated a significant weight loss for the Swedish adjustable gastric band (SAGB). PATIENTS AND METHODS: Between November 1996 and April 1998, 18 morbidly obese patients underwent SAGB laparoscopically. Their mean age at surgery was 35 years. The mean preoperative weight was 128 kg (range 89-163), and the mean body mass index was 50.4+/-9. Comorbidity was present in 13 patients. RESULTS: One gastric perforation occurred, and in one patient it was not possible to create the pneumoperitoneum. Regarding late morbidity, one intragastric migration and one slippage of the band occurred. There was no mortality. CONCLUSION: The low morbidity, the good results with weight loss, and the improvement in comorbidity lead the authors to believe that Swedish adjustable gastric banding for the treatment of morbidly obese patients is a successful means of losing weight and improving general health.