RESUMEN
Five new cyclic peptoids containing (2S,4R)-4-hydroxyproline (Hyp) residues have been designed and synthesized using a mixed "submonomer/monomer" approach. Alkali metal cation affinities and ion transport activities were assessed by experimental (NMR and HPTS assay in liposomes) and computational methods. Easy functionalization of hydroxyproline residues afforded a bouquet of cyclic oligomers showing correlation between ion transport abilities and cytotoxic activities on selected human cancer cell lines.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Hidroxiprolina/química , Peptoides/química , Peptoides/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Sodio/químicaRESUMEN
Most of the structural studies made on the secondary structure of peptoids describe their geometric attributes in terms of the classic Ramachandran plot (based on the local analysis of ω, ψ, χ, φ dihedral angles). However, little intuitive understanding is available from internal coordinates when stereochemistry is involved. In this contribution we list all the conformationally stable cyclic peptoids reported up to the year 2017 and propose a simple method to define their geometric arrangement in terms of planar chirality. Evidence of conformational isomerism (due to the long average time of single bond rotation) and conformational chirality (induced by the absence of roto-reflection axes) in this promising class of synthetic macrocycles is provided by NMR spectroscopy (using Pirkle's alcohol as chiral solvating agent) and careful evaluation of X-ray crystallographic studies. The full understanding of the oligomeric macrocycles' structural properties and the clear framing of their conformational isomerism in a proper conceptual scheme is fundamental for future application of peptoids in asymmetric synthesis, chiral recognition and supramolecular chemistry.
Asunto(s)
Peptoides/química , Cristalografía por Rayos X , Modelos Moleculares , Conformación Proteica , EstereoisomerismoRESUMEN
An efficient protocol for the solid-phase synthesis of six members of a new class of extended macrocyclic peptoids (based on ortho-, meta- and para-N-(methoxyethyl)aminomethyl phenylacetyl units) is described. Theoretical (DFT) and experimental (NMR) studies on the free and Na+-complexed cyclic trimers (3-5) and tetramers (6-8) demonstrate that annulation of the rigidified peptoids can generate new hosts with the ability to sequestrate one or two sodium cations with the affinities and stoichiometries defined by the macrocycle morphology. Ion transport studies have been also performed in order to better appreciate the factors promoting transmembrane cation translocation.
Asunto(s)
Compuestos de Bencilo/síntesis química , Ionóforos/síntesis química , Compuestos Macrocíclicos/síntesis química , Peptoides/síntesis química , Compuestos de Bencilo/química , Ciclización , Transporte Iónico , Ionóforos/química , Compuestos Macrocíclicos/química , Modelos Moleculares , Peptoides/química , Sodio/químicaRESUMEN
This study assessed changes in prevalence and distribution of HIV-1 non-subtype B viruses in Italian and immigrant patients over two decades in a province in Italy. All HIV-positive patients who underwent genotypic resistance testing were selected. Prevalence of non-subtype B viruses in 3-year periods was calculated. All sequences of non-subtype B and those provided by REGA as unassigned were analysed for phylogenetic relationships. In total, 250/1563 (16%) individuals were infected with a non-subtype B virus. Prevalence increased over time, reaching a peak (31.5%) in 2004-2006. In Italian patients, the most frequent subtypes were B (92.5%) and F1 (4%). F1 subtype was also prevalent in patients from South America (13.6%); in patients of African origin, CRF02_AG (54.9%) and G (12.3%) were the most frequent. HIV-1 non-subtype B infections in Italians were mostly found in patients who acquired HIV sexually. A phylogenetic relationship between F subtypes in Italian and representative HIV-1 sequences from Brazil was found. C subtypes in Italians were phylogenetically related to subtypes circulating in Brazil. Inter-subtype recombinants were also found in the latest years. The HIV-1 epidemic in Brescia province evolved to the point where about 1/3 patients recently diagnosed harboured non-B HIV subtypes. The distribution of HIV-1 non-B subtypes in Italian patients resembled that in South American patients and phylogenetic relatedness between some Italian and South American HIV-1 strains was found. The possible epidemiological link between these two populations would have been missed by looking only at risk factors for HIV acquisition declared by patients. The evidence of inter-subtype recombinants points to significant genetic assortment. Overall our results support phylogenetic analysis as a tool for epidemiological investigation in order to guide targeted prevention strategies.
Asunto(s)
Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/clasificación , Adulto , Distribución de Chi-Cuadrado , Femenino , Genotipo , Infecciones por VIH/etnología , Infecciones por VIH/genética , VIH-1/genética , Humanos , Italia/epidemiología , Modelos Logísticos , Masculino , Epidemiología Molecular , Filogenia , Prevalencia , Análisis de Secuencia de ADNRESUMEN
N-Benzyloxyethyl cyclic alpha-peptoids of various size were prepared and their conformational features were investigated by means of computational, spectroscopic, and X-ray crystallographic studies.
Asunto(s)
Péptidos Cíclicos/química , Cristalografía por Rayos X , Modelos Moleculares , Resonancia Magnética Nuclear Biomolecular , Péptidos Cíclicos/síntesis química , Conformación ProteicaRESUMEN
This chapter covers the synthetic aspects of both linear or cyclic peptides and depsipeptides isolated from opisthobranch molluscs. In many cases, synthetic effort not only determined the absolute stereostructure of these compounds but also made it possible to supply sufficient amounts for the evaluation of pharmacological activities. A summary of the synthetic work associated with each compound is reported after a short description of its natural source and biological properties. Discussion in the text concentrates on key reactions and synthetic efficiency.
Asunto(s)
Factores Biológicos/química , Productos Biológicos/síntesis química , Depsipéptidos/química , Biología Marina , Moluscos/química , Péptidos/química , Animales , Factores Biológicos/síntesis química , Depsipéptidos/síntesis químicaRESUMEN
A quantitative measurement of laser-beam quality can be performed by determination of the presence of multiple transverse modes of the laser oscillator and by calculation of their power content. Along this line of argument, we discuss a new approach that, starting from near-field and far-field intensity measurements, can evaluate the complex excitation coefficients of the transverse modes in a laser beam. The exploitation of near-field measurements sharply improves the performances of the technique in those cases in which only far-field measurements are used. The validity of the method is confirmed by several accurate numerical simulations and by some experimental results relative to a multimode Q-switched Nd:YAG laser.
RESUMEN
The Harderian gland of the green frog contains mast cells. Their number shows annual variations, being more numerous in the winter months. The increase of mast cell number (MCN) is matched by a marked degranulation. No sex differences are found throughout the year. Manipulations of the photoperiod and temperature, either in winter or in summer, suggest that only the latter is responsible for the annual variations. Exposure to higher temperatures causes a decrease in the MCN in the winter frogs, while exposure of the summer frogs to low temperatures provokes the opposite effect. The pituitary gland also influences MCN. Hypophysectomy causes a decrease of MCN, with a return to normal following replacement therapy with homologous pars distalis homogenate. Among pituitary hormones, only ACTH mimics the effect of pars distalis homogenate. However, a possible link seems to exist between environmental (temperature) and hormonal (pituitary) factors, since hypophysectomy prevents the increase of MCN in the summer frogs exposed to low temperatures.