1,720,979 research outputs found
Lights on 2,5-diaryl tetrazoles: applications and limits of a versatile photoclick reaction
No full textRecently, photoclick chemistry emerged as a powerful tool employed in several research fields, from medicinal chemistry and biology to material sciences. The growing interest in this type of chemical process is justified by the possibility to produce complex molecular systems using mild reaction conditions. However, the elevated spatio-temporal control offered by photoclick chemistry is highly intriguing, as it expands the range of applications. In this context, the light-triggered reaction of 2,5-diaryl tetrazoles with dipolarophiles emerged for its interesting features: excellent stability of the substrates, fast reaction kinetic, and the formation of a highly fluorescent product, fundamental for sensing applications. In the last years, 2,5-diaryl tetrazoles have been extensively employed, especially for bioorthogonal ligations, to label biomolecules and nucleic acids. In this review, we summarized recent applications of this interesting photoclick reaction, with a particular focus on biological fields. Moreover, we described the main limits that affect this system and current strategies proposed to overcome these issues. The general discussion here presented could prompt further optimization of the process and pave the way for the development of new original structures and innovative applications
An overview of quadruplex ligands: Their common features and chemotype diversity
No full textG-quadruplexes (G4s), guanine-rich sequences that are able to fold up in polymorphous secondary structures, have received increasing attention in medicinal chemistry thanks to their occurrence in “hot” regions of the genome. Indeed, there is much evidence that G4s affect genomic instability, telomerase dysfunction, and behave as transcriptional repressor elements. Thus, targeting G4 structures has emerged as an alternative strategy for the potential treatment of several diseases. This chapter offers an overview of the critical role that the rational design of molecular ligands able to selectively interact, stabilize and cleave G4s, could play in drug discovery. Starting from natural products to more recent synthetic compounds, the key structural differences as well as the common features of each ligands sub-category have been compared to provide general directions in the development of more efficient and bioactive G4 ligands
Multimeric G-quadruplexes: A review on their biological roles and targeting
Full text linkIn human cells, nucleic acids adopt several non-canonical structures that regulate key cellular processes. Among them, G-quadruplexes (G4s) are stable structures that form in guanine-rich regions in vitro and in cells. G4 folded/unfolded state shapes numerous cellular processes, including genome replication, transcription, and translation. Moreover, G4 folding is involved in genomic instability. G4s have been described to multimerize, forming high-order structures in both DNA and/or RNA strands. Multimeric G4s can be formed by adjacent intramolecular G4s joined by stacking interactions or connected by short loops. Multimeric G4s can also originate from the assembly of guanines embedded on independent DNA or RNA strands. Notably, crucial regions of the human genome, such as the 3′-terminal overhang of the telomeric DNA as well as the open reading frame of genes involved in the preservation of neuron viability in the human central and peripheral nervous system are prone to form multimeric G4s. The biological importance of such structures has been recently described, with multimeric G4s playing potentially protective or deleterious effects in the pathogenic cascade of various diseases. Here, we portray the multifaceted scenario of multimeric G4s, in terms of structural properties, biological roles, and targeting strategies
The Quest for the Right Trade-Off for an Efficient Photoclick Monitoring Reaction
No full textPhotoinduced cycloaddition of 2,5-diaryltetrazoles with alkenes, to produce 2,5-diarylpyrazolines, has been widely exploited as orthogonal ligation for bio-labeling and cross-linking. This reaction is particularly interesting and useful, as it combines mild activation conditions to the generation of a fluorescent product. However, it suffers from two major drawbacks, as under physiological conditions hydration by-products are formed and the fluorescent quantum yield of the emitting pyrazoline is often reduced in water. In this work, we have thoroughly investigated both the photoreactivity of a small library of water soluble tetrazoles and the optical properties of the resulting pyrazolines, to optimize both chemical selectivity (cycloaddition vs hydration) and photo-physical efficiency. Electron-withdrawing (A) and electron-donating (D) substituents tune pyrazoline reaction yields and their fluorescence quantum yields in opposite directions. The combination of two D-substituents on the tetrazoles ensures quantitative pyrazoline formation with low emission. On the contrary, two A-substituents afforded very emitting pyrazolines in low chemical yield. We have identified the water-soluble tetrazole T7 as the best compromise, able to afford a highly fluorescent pyrazoline, in high yields
Photoresponsive molecular devices targeting nucleic acid secondary structures
No full textNon B-DNA structures are non-canonical nucleic acid conformations adopted by single strands fulfilling specific sequence requirements. Numerous experimental evidences support their roles as regulators of biological processes, involving genetic information transfer. However, direct visualization of the folding and unfolding of such structures in live cells still remains elusive, as well as a detailed understanding of their mechanisms of action and functions. Fluorescent light-up probes are excellent tools to address these pending questions. This review aims at classifying the multitude of dyes available to date in terms of operating mechanism (conformational restriction, TICT, aggregation related phenomena, conjugation, etc.) and targeted structures. The most promising results are presented for each conformational class, contextually highlighting the main criticalities and the remaining gaps
Dna binding mode analysis of a core-extended naphthalene diimide as a conformation-sensitive fluorescent probe of g-quadruplex structures
No full textG-quadruplex existence was proved in cells by using both antibodies and small molecule fluorescent probes. However, the G-quadruplex probes designed thus far are structure-but not conformation-specific. Recently, a core-extended naphthalene diimide (cex-NDI) was designed and found to provide fluorescent signals of markedly different intensities when bound to G-quadruplexes of different conformations or duplexes. Aiming at evaluating how the fluorescence behaviour of this compound is associated with specific binding modes to the different DNA targets, cex-NDI was here studied in its interaction with hybrid G-quadruplex, parallel G-quadruplex, and B-DNA duplex models by biophysical techniques, molecular docking, and biological assays. cex-NDI showed different binding modes associated with different amounts of stacking interactions with the three DNA targets. The preferential binding sites were the groove, outer quartet, or intercalative site of the hybrid G-quadruplex, parallel G-quadruplex, and B-DNA duplex, respectively. Interestingly, our data show that the fluorescence intensity of DNA-bound cex-NDI correlates with the amount of stacking interactions formed by the ligand with each DNA target, thus providing the rationale behind the conformation-sensitive properties of cex-NDI and supporting its use as a fluorescent probe of G-quadruplex structures. Notably, biological assays proved that cex-NDI mainly localizes in the G-quadruplex-rich nuclei of cancer cells
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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