Preparation of penta-azole containing cyclopeptides: challenges in macrocyclization

Herein is described the synthesis of several analogs of the natural product IB-01211 from concatenated azoles, via a biomimetic pathway based on cyclization-oxidation of serine containing peptides combined with the Hantzsch synthesis. The macrocyclization of rigid peptide compounds 1 and 2 to give IB-01211 and its epimer 12b was explored, and the results are compared here to those previously obtained for the macrocyclization of more flexible structures in the syntheses of YM-216391, telomestatin, and IB-01211. Lastly, the preliminary results of anti-tumor activity screening of the synthesized analogs are discussed.

Total synthesis and antiproliferative activity screening of (±)-aplicyanins A, B and E and related analogs

The first total synthesis of the indole alkaloids ()-aplicyanins A, B and E, plus seventeen analogs, all in racemic form is reported. Modifications to the parent compound included changing the number of bromine substituents on the indole, the groups on the indole nitrogen (H, Me or OMe), and/or the oxidation level of the heterocyclic core tetrahydropyrimidine. Each compound was screened against three human tumor cell lines, and fourteen of the newly synthesized compounds showed considerable cytotoxicity. The assay results were used to establish structure-activity relationships. These results suggest that the acetyl group moiety on the imine nitrogen, and the bromine at position 5 of the indole, are both critical to activity.

Synthesis and antitumor activity of mechercharmycin A analogues

Several analogs of the cytotoxic thiopeptide IB-01211 or Mechercharmycin A (1) have been synthetized. The cytotoxicity of 1 and the synthetized analogs was evaluated against a panel of three human tumor cell lines. Thiopeptide 1 and the most active derivatives, 2 and 3c, were chosen for further studies like effects on cell cycle progression and induction of apoptosis. Interestingly, the inhibition of cell division and activation of a programmed cell death by apoptosis was detected.

Arduino Tricorder : Aplicació Android per a la supervisió, control i adquisició de dades d'una placa Arduino

Aplicació Android per a la supervisió, control i adquisició de dades d'una placa Arduino que disposi de comuninació Ethernet i/o Wi-Fi. Creació d'interfícies dinàmiques amb diferents modalitats d'interacció: tàctil, reconeixement de veu i síntesi de veu.

Ligações hidrogênio fortes em ácidos dicarboxílicos e diaminas aromáticas

A very short-strong hydrogen bond (<2 Å, >20kcal/mol) is found in the monoanion of certain dicarboxylic acids derived from maleic and dialkylmalonic acids. Certain aromatic diamines that are known as proton sponge have exceptionally high basicity (pKa) and are only monoprotonated with strong acids like percloric acid. The closed proximity between the two basic centers provokes a strong steric interaction that is relieved upon protonation. Similar effects are found in dicarboxylic acids (hydrogen maleate and hydrogen dialkylmalonates) that present a very short distance between the two oxygens and a short-strong hydrogen bond.

Actualidad de la Idea de una universidad de J. H. Newman

A mitjans de segle XIX, John Henry Newman va rebre l'encàrrec d'organitzar i dirigir una nova universitat a Dublin. Com a síntesi de les reflexions que van acompanyar aquell projecte, va publicar un escrit intitulat Idea of a University que encara avui dia ofereix nombrosos elements per a la reflexió de tots aquells que en formem part de la comunitat universitària. Els trets distintius de la universitat en què Newman hi pensa són: una vocació humil de servei que es concreta en la formació de persones, no tant de gentlemen o elits socials; primacia de l'educació de la intel·ligència especulativa, sense subordinar-la a l'educació moral ni a la formació tècnica; un lloc d'ensenyament del saber universal -deixant per altres institucions l'activitat de pura investigació- i de contacte viu entre les diferents especialitats -és bàsic l'intercanvi continu d'experiències entre docents i alumnes d'estudis diferents-; una acció tutorial que permeti descobrir en cada alumne els seus talents i les seves aptituds particulars; una producció o 'transferència de coneixement' vinculada a la vàlua real de l'activitat intel·lectual -qui publica ho fa perquè realment té quelcom a dir-. Com a rerefons d'aquestes propostes, Newman posa l'accent en la necessitat que la universitat sigui un ambient on es confia pregonament en la possibilitat d'accedir a un coneixement veritable de la realitat. Més que mai en un món intel·lectual que ja a mitjans segle XIX començava a trontollar sota el pes del nihilisme i l'escepticisme, Newman reivindica el valor de la veritat com a fi últim de tota vida universitària.

Membrane interaction of a new synthetic antimicrobial lipopetide sp-85 with broad spectrum activity

Antimicrobial peptides offer a new class of therapeutic agents to which bacteria may not be able todevelop genetic resistance, since their main activity is in the lipid component of the bacterial cell mem-brane. We have developed a series of synthetic cationic cyclic lipopeptides based on natural polymyxin,and in this work we explore the interaction of sp-85, an analog that contains a C12 fatty acid at theN-terminus and two residues of arginine. This analog has been selected from its broad spectrum antibac-terial activity in the micromolar range, and it has a disruptive action on the cytoplasmic membrane ofbacteria, as demonstrated by TEM. In order to obtain information on the interaction of this analog withmembrane lipids, we have obtained thermodynamic parameters from mixed monolayers prepared withPOPG and POPE/POPG (molar ratio 6:4), as models of Gram positive and Gram negative bacteria, respec-tively. LangmuirBlodgett films have been extracted on glass plates and observed by confocal microscopy,and images are consistent with a strong destabilizing effect on the membrane organization induced bysp-85. The effect of sp-85 on the membrane is confirmed with unilamelar lipid vesicles of the same com-position, where biophysical experiments based on fluorescence are indicative of membrane fusion andpermeabilization starting at very low concentrations of peptide and only if anionic lipids are present.Overall, results described here provide strong evidence that the mode of action of sp-85 is the alterationof the bacterial membrane permeability barrier.

The synthesis of 1,2,3,6,6a,7-hexahydro-7-methyl-5-imino-1H-pyrrolo[1,2-c]imidazolo[5,4-b]indole

N-3-(1-Methylindol-3-yl)propan-N-(2,2,2-trichloroethoxysulfonyl)guanidine was synthesized from 3-formyl-1-methylindole in six steps and subjected to conditions intended to convert the side-chain into a 2-iminotetrahydropyrimidine- containing product, of relevance to a possible synthesis of the aplicyanins. An alternative reaction course was observed, resulting in the formation of a new tetracyclic system.

Selenomethionine incorporation into amyloid sequences regulates fibrillogenesis and toxicity.

The capacity of a polypeptide chain to engage in an amyloid formation process and cause a conformational disease is contained in its sequence. Some of the sequences undergoing fibrillation contain critical methionine (Met) residues which in vivo can be synthetically substituted by selenomethionine (SeM) and alter their properties.

L'entonació dels titulars de les notícies en català. Trets melòdics dels locutors

En aquest article descrivim les tendències entonatives que caracteritzen la locució dels titulars de les notícies per mitjà de sis de les veus més conegudes de la televisió catalana (tv3 i 3/24): Xavier Coral, Agnès Marquès, Ramon Pellicer, Joan Carles Peris, Raquel Sans i Núria Solé. Per portar a terme la investigació, ens hem basat en el mètode Anàlisi Melòdica de la Parla, descrit a Cantero (2002), i hem utilitzat l'aplicació d'anàlisi i síntesi de veu Praat. Prenent com a base els patrons melòdics i els èmfasis de la parla espontània del català, hem constatat que per a aquest tipus de locució, pròpia d'un registre formal, solament es fan servir de forma continuada i repetitiva una part dels trets melòdics ja descrits, amb la qual cosa s'aconsegueix un efecte característic que la fa singular i la distancia de la parla espontània. També hem descrit els trets melòdics que tenen en comú els sis locutors i els trets en què difereixen.

The synthesis of 1,2,3,6,6a,7-hexahydro-7-methyl-5-imino-1H-pyrrolo[1,2-c]imidazolo[5,4-b]indole

N-3-(1-Methylindol-3-yl)propan-N-(2,2,2-trichloroethoxysulfonyl)guanidine was synthesized from 3-formyl-1-methylindole in six steps and subjected to conditions intended to convert the side-chain into a 2-iminotetrahydropyrimidine- containing product, of relevance to a possible synthesis of the aplicyanins. An alternative reaction course was observed, resulting in the formation of a new tetracyclic system.

Coneixement i indústria

En síntesi, l'economia del coneixement, per la qual hem d'apostar, no és eliminar la indústria, és una cosa ben diferent. Apostar per la recerca i la innovació sí, però també una indústria forta que les integri. El govern explica en el seu pla d'acció que s'han identificat i definit set àmbits en els quals centrarà les seves prioritats en política industrial i orientarà les seves accions

Synthetic approaches towards the Lycopodium alkaloids

The Lycopodium alkaloids are a structurally diverse group of natural products isolated from Lycopodium with important biological effects for the potential treatment of cancer and severe neurodegenerative diseases. To date, full biological studies have been hampered by lack of material from natural sources. Total synthesis represents a possible solution to meet this demand as well as the most effective way to design new compounds to determine structural activity relationships and obtain more potent compounds. The aim of this chapter is to summarise the work carried out in this field so far by presenting an overview of the synthetic strategies used to access each of the four key Lycopodium alkaloid types. Particular emphasis has been placed on methods that rapidly construct each nucleus utilizing tandem reactions.

Synthetic approaches towards the Lycopodium alkaloids

The Lycopodium alkaloids are a structurally diverse group of natural products isolated from Lycopodium with important biological effects for the potential treatment of cancer and severe neurodegenerative diseases. To date, full biological studies have been hampered by lack of material from natural sources. Total synthesis represents a possible solution to meet this demand as well as the most effective way to design new compounds to determine structural activity relationships and obtain more potent compounds. The aim of this chapter is to summarise the work carried out in this field so far by presenting an overview of the synthetic strategies used to access each of the four key Lycopodium alkaloid types. Particular emphasis has been placed on methods that rapidly construct each nucleus utilizing tandem reactions.

Interpretación ambiental de INBioparque, La Finca (Costa Rica)

Este artículo es una síntesis del proyecto realizado en INBio (Instituto Nacional de Biodiversidad), Costa Rica, cuyo objetivo principal fue la mejora de la Interpretación Ambiental de INBioparque, un parque temático de biodiversidad dentro de la institución. INBioparque está situado en Santo Domingo de Heredia, provincia de Heredia, Costa Rica. Éste pretende hacer una pequeña representación de los principales ecosistemas que se encuentran en el país. El parque se divide en diferentes zonas: Bosque del Valle Central, Bosque Húmedo, Bosque Seco, Humedal y Finca. En esta última, la Finca (ecosistema basado en la biodiversidad domesticada) es dónde se ha centrado todo el proyecto, debido a que presentaba una mayor necesidad de mejora en su interpretación ambiental. La Interpretación ambiental traduce el lenguaje técnico de los profesionales a términos e ideas más entendedoras para todos los públicos. Pretende promover una nueva conciencia sobre el valor de la biodiversidad, lograr su conservación y mejorar la calidad de vida del ser humano. El proyecto propone la mejora de la interpretación ambiental a través de las fichas técnicas elaboradas de las diferentes especies vegetales de la Finca, así como la renovación o creación de rótulos explicativos. Se propone también un recorrido guiado y auto guiado para hacer más entendedora la visita, además de algunas actividades y talleres.