Orthogonal protection of peptides and peptoids for cyclization by the thiol-ene reaction and conjugation

Cyclic peptides and peptoids were prepared using the thiolene Michael-type reaction. The linear precursors were provided with additional functional groups allowing for subsequent conjugation: an orthogonally protected thiol, a protected maleimide, or an alkyne. The functional group for conjugation was placed either within the cycle or in an external position. The click reactions employed for conjugation with suitably derivatized nucleoside or oligonucleotides were either cycloadditions (Diels-Alder, Cu(I)-catalyzed azide-alkyne) or the same Michael-type reaction as for cyclization.

Dynamic range extension of SiPM detectors with the time-gated operation

The silicon photomultiplier (SiPM) is a novel detector technology that has undergone a fast development in the last few years, owing to its single-photon resolution and ultra-fast response time. However, the typical high dark count rates of the sensor may prevent the detection of low intensity radiation fluxes. In this article, the time-gated operation with short active periods in the nanosecond range is proposed as a solution to reduce the number of cells fired due to noise and thus increase the dynamic range. The technique is aimed at application fields that function under a trigger command, such as gated fluorescence lifetime imaging microscopy.

Applications of optically active metallacycles: new useful materials for the determination of the enantiomeric excess of Lewis bases and as resolving agents for monodentate phosphines

Es descriu la síntesi de nous compostos ciclopal·ladats derivats d'imines i amines primàries, òpticament actius, així com les seves aplicacions per a la determinació de l'excés enantiomèric i per a la resolució de bases de Lewis. També es comenta la síntesi i resolució de noves fosfines P-quirals, així com la seva aplicació a processos de catàlisi asimètrica. A més, es descriu la preparació d'algunes fosfines secundàries quirals i s'estudia la seva estabilitat configuracional.

Easy introduction of maleimides at different positions of oligonucleotide chains for conjugation purposes

[2,5-Dimethylfuran]-protected maleimides were placed at both internal positions and the 3'-end of oligonucleotides making use of solid-phase synthesis procedures. A new phosphoramidite derivative and a new solid support incorporating the protected maleimide moiety were prepared for this purpose. In all cases maleimide deprotection (retro-Diels-Alder reaction) followed by reaction with thiol-containing compounds afforded the target conjugate.

Conjugation reactions involving maleimides and phosphorothioate oligonucleotides

Phosphorothioate diester oligonucleotides proved to be fully compatible with maleimides in the context of two different conjugation reactions: (a) reaction of 5′diene-[phosphorothioate oligonucleotides] with maleimido-containing compounds to afford the Diels-Alder cycloadduct; (b) conjugation of 5′maleimido-[phosphorothioate oligonucleotides] with thiol-containing compounds. No evidence of reaction between phosphorothioate diesters and maleimides was found in any of these processes. Importantly, in the preparation of 5′maleimido-[phosphorothioate oligonucleotides] from [protected maleimido]-[phosphorothioate oligonucleotides], which requires the maleimide to be deprotected by retro-Diels-Alder reaction (heating for 3-4 h in toluene at 90 °C), no addition of phosphorothioate diester to the maleimide was found either. Finally, maleimide-[phosphorothioate monoester] conjugation was also explored for comparison purposes.

Readout schemes for low noise single-photon avalanche diodes fabricated in conventional HV-CMOS technologies

Three different pixels based on single-photon avalanche diodes for triggered applications, such as fluorescence lifetime measurements and high energy physics experiments, are presented. Each pixel consists of a 20µm x 100µm (width x length) single photon avalanche diode and a monolithically integrated readout circuit. The sensors are operated in the gated mode of acquisition to reduce the probability to detect noise counts interferring with real radiation events. Each pixel includes a different readout circuit that allows to use low reverse bias overvoltages. Experimental results demonstrate that the three pixels present a similar behaviour. The pixels get rid of afterpulses and present a reduced dark count probability by applying the gated operation. Noise figures are further improved by using low reverse bias overvoltages. The detectors exhibit an input dynamic range of 13.35 bits with short gated"on" periods of 10ns and a reverse bias overvoltage of 0.5V. The three pixels have been fabricated in a standard HV-CMOS process.

Dynamic range extension of SiPM detectors with the time-gated operation

The silicon photomultiplier (SiPM) is a novel detector technology that has undergone a fast development in the last few years, owing to its single-photon resolution and ultra-fast response time. However, the typical high dark count rates of the sensor may prevent the detection of low intensity radiation fluxes. In this article, the time-gated operation with short active periods in the nanosecond range is proposed as a solution to reduce the number of cells fired due to noise and thus increase the dynamic range. The technique is aimed at application fields that function under a trigger command, such as gated fluorescence lifetime imaging microscopy.

Ocupa-la palabra

Abonda con repasa-los manuais de historia da literatura galega para comprobar que a presencia feminina de certo releyo queda limitada a unha figura sobranceira, Rosalía de Castro, que logo foi acompañándose de Pura Vázqtíez, Luz Pozo Garza, Xohana Torres ou Maria Xosé Queízan. Poucas máis son as escritoras galegas de antes de 1976 que tiveron acceso 6 recoñecemento xeral. Cerramenre este mangado de nomes é máis ben caríveiro en comparación coa longa restra de autores masculinos, pero resulta moito máis rechamante se o comparamos co grande pulo que está a te-la poesía de muller hoxe en día; un pulo moito maior ca noutros xéneros, e aínda así moi por detrás da literatura infantil e da crítica literaria. A presencia destacada da muller nestes ámbitos lévanos, necesariamente, a constara-lo efecto espello que se produce entre a súa situación social e os xéneros literarios ós que semella ter un acceso máis doado...

Ocupa-la palabra

Abonda con repasa-los manuais de historia da literatura galega para comprobar que a presencia feminina de certo releyo queda limitada a unha figura sobranceira, Rosalía de Castro, que logo foi acompañándose de Pura Vázqtíez, Luz Pozo Garza, Xohana Torres ou Maria Xosé Queízan. Poucas máis son as escritoras galegas de antes de 1976 que tiveron acceso 6 recoñecemento xeral. Cerramenre este mangado de nomes é máis ben caríveiro en comparación coa longa restra de autores masculinos, pero resulta moito máis rechamante se o comparamos co grande pulo que está a te-la poesía de muller hoxe en día; un pulo moito maior ca noutros xéneros, e aínda así moi por detrás da literatura infantil e da crítica literaria. A presencia destacada da muller nestes ámbitos lévanos, necesariamente, a constara-lo efecto espello que se produce entre a súa situación social e os xéneros literarios ós que semella ter un acceso máis doado...

Protected maleimide building blocks for the decoration of peptides, peptoids and peptide nucleic acids

Monomers allowing for the introduction of [2,5-dimethylfuran]-protected maleimides into polyamides such as peptides, peptide nucleic acids, and peptoids were prepared, as well as the corresponding oligomers. Suitable maleimide deprotection conditions were established in each case. The stability of the adducts generated by Michael-type maleimide-thiol reaction and Diels-Alder cycloaddition to maleimide deprotection conditions was exploited to prepare a variety of conjugates from peptide and PNA scaffolds incorporating one free and one protected maleimide. The target molecules were synthesized by using two subsequent maleimide-involving click reactions separated by a maleimide deprotection step. Carrying out maleimide deprotection and conjugation simultaneously gave better results than performing the two reactions subsequently.

Straightforward synthesis of cyclic and bicyclic peptides

Cyclic peptide architectures can be easily synthesized from cysteine-containing peptides with appending maleimides, free or protected, through an intramolecular Michael-type reaction. After peptide assembly, the peptide can cyclize either during the trifluoroacetic acid treatment, if the maleimide is not protected, or upon deprotection of the maleimide. The combination of free and protected maleimide moieties and two orthogonally protected cysteines gives access to structurally different bicyclic peptides with isolated or fused cycles.

Oligonucleotide cyclization: The thiol-maleimide reaction revisited

A novel method to synthesize cyclic oligonucleotides (5- to 26-mer) using the thiol-maleimide reaction is described. The target molecules were obtained after subsequent removal of thiol and maleimide protecting groups from 5′-maleimido-3′-thiol-derivatized linear precursors. Retro-Diels-Alder conditions deprotecting the maleimide simultaneously promoted cyclization cleanly and in high yield.