Straightforward method for the preparation of lysine-based double-chained anionic surfactants

Double-chained surfactants with potential biocompatibility have been prepared in high yields by lysine acylation with four natural saturated fatty acids (C(6) to C(12)) and with cis-undec-5-enoic acid. The surfactants were found to assemble into nanotubules in aqueous medium and, when mixed with a commercial cationic surfactant, to spontaneously form liposomes

Phenolic quantification and botanical origin of Portuguese propolis

The production of propolis by honeybees results from a selective collection of exudates from leaf buds and plants present in the hive neighborhood leading to a resin with many potentialities in the pharmaceutical industry. This study aims to quantify the phenolic content in propolis from different Portuguese regions and in the potential floral sources, Populus x Canadensis Moench buds and Cistus ladanifer L., in order to establish links with geographical and botanical origin. The Portuguese propolis revealed a phenolic profile with marked differences in concentrations: the richness in flavonoids is common in all regions, but more evident in propolis from central interior, south and Madeira. The composition of poplar type propolis common in temperate zones was observed in the north, central coast and Azores, while the central interior and south samples, with a composition rich in kaempferol derivatives, resemble the C. ladanifer exudates, a spontaneous bush widespread in the Mediterranean. The compound kaempferol-3,7-dimethyl-ether, absent in the poplar type propolis, can be regard as a possible marker for the discrimination of these two types of propolis

Melanoma targeting with alpha-melanocyte stimulating hormone analogs labeled with fac-[Tc-99m(CO)(3)](+): effect of cyclization on tumor-seeking properties

Early detection of primary melanoma tumors is essential because there is no effective treatment for metastatic melanoma. Several linear and cyclic radiolabeled alpha-melanocyte stimulating hormone (alpha-MSH) analogs have been proposed to target the melanocortin type 1 receptor (MC1R) overexpressed in melanoma. The compact structure of a rhenium-cyclized alpha-MSH analog (Re-CCMSH) significantly enhanced its in vivo tumor uptake and retention. Melanotan II (MT-II), a cyclic lactam analog of alpha-MSH (Ac-Nle-cyclo[Asp-His-DPhe-Arg-Trp-Lys]-NH2]), is a very potent and stable agonist peptide largely used in the characterization of melanocortin receptors. Taking advantage of the superior biological features associated with the MT-II cyclic peptide, we assessed the effect of lactam-based cyclization on the tumor-seeking properties of alpha-MSH analogs by comparing the pharmacokinetics profile of the (99)mTc-labeled cyclic peptide beta Ala-Nle-cyclo[Asp-His-DPhe-Arg-Trp-Lys]-NH2 with that of the linear analog beta Ala-Nle-Asp-His-DPhe-Arg-Trp-Lys-NH2 in melanoma-bearing mice. We have synthesized and coupled the linear and cyclic peptides to a bifunctional chelator containing a pyrazolyl-diamine backbone (pz) through the amino group of beta Ala, and the resulting pz-peptide conjugates were reacted with the fac-[Tc-99m(CO)(3)](+) moiety. The Tc-99m(CO)(3)-labeled conjugates were obtained in high yield, high specific activity, and high radiochemical purity. The cyclic Tc-99m(CO)(3)-labeled conjugate presents a remarkable internalization (87.1% of receptor-bound tracer and 50.5% of total applied activity, after 6 h at 37 degrees C) and cellular retention (only 24.7% released from the cells after 5 h) in murine melanoma B16F1 cells. A significant tumor uptake and retention was obtained in melanoma-bearing C57BL6 mice for the cyclic radioconjugate [9.26 +/- 0.83 and 11.31 +/- 1.83% ID/g at 1 and 4 h after injection, respectively]. The linear Tc-99m(CO)(3)-pz-peptide presented lower values for both cellular internalization and tumor uptake. Receptor blocking studies with the potent (Nle(4),DPhe(7))-alpha MSH agonist demonstrated the specificity of the radioconjugates to MC1R (74.8 and 44.5% reduction of tumor uptake at 4 h after injection for cyclic and linear radioconjugates, respectively)

Self-assembly in a catanionic mixture with an aminoacid-derived surfactant: From mixed micelles to spontaneous vesicles

The aqueous self-assembly of a novel lysine-derived surfactant with a gemini-like architecture, designated here as 12-Lys-12, has been experimentally investigated for the amphiphile alone in water and in a mixture with dodecyltrimethylammonium bromide (DTAB). The neat surfactant forms interesting micrometer-sized rigid tubules in the dilute region, resulting in very viscous solutions. For the catanionic mixture with DTAB, various single and multiphase regions were identified (up to a total surfactant concentration of 1.5 wt %) by means of combined polarizing light microscopy, cryo-TEM, and NMR. In the DTAB-rich side, for a mixing molar ratio in the range 2 < DTAB/12-Lys-12 < 4, a region of stable, unilamellar vesicles can be found. Furthermore, it was found that upon addition of 12-Lys-12 to pure DTAB solutions, the mixed micelles grow and beyond a given mixing ratio, vesicles assemble and coexist with small micelles. The transition is not continuous, since there is a narrow mixing range where phase separation occurs. Self-diffusion measurements and cryo-TEM imaging show that the average vesicle radius is on the order of 30-40 nm