1,720,982 research outputs found
Pyrazolo-isothiazole dioxide: an interesting scaffold for the preparation of peptidomimetics
No full textThere are many examples in literature of peptidomimetics that incorporate a heterocycle scaffold into a peptide, or a peptide-like sequence. The pre-organization of peptide shape, via the introduction of a structural heterocyclic motif that imparts conformational restriction, can enhance binding and hence therapeutic potential.1
Hitherto the standard approach to combine heterocycles and peptides has been to functionalize the side chain or the N/C termini of an amino acid building block with the heterocyclic moiety.2 A few examples have been accomplished in which the heterocycles are part of the peptide backbone itself.3
By the way of a 1,3-dipolar cycloaddition reaction between diazoacetates 2 and the high reactive double bond of the 3-amino isothiazole dioxide partner 1, the adducts 3 are obtained in high yield and complete regioselectivity.
The presence in compounds 3 of the carboxylic substituent and the pyrazole NH group can be exploited for coupling reaction with amino acids. By this way a peptide sequence can be generated characterized by the rigid planar geometry of the heterocyclic system favoring a particular orientation of the growing peptide chain (Figure).
Moreover the presence of the sulfonyl group as well as the NH group at C-3 is of interest. They can behave as hydrogen bond acceptor and donor, respectively, giving raise to interactions with proteins or other potential targets.
The synthesis of model peptidomimetics containing the heterocyclic scaffold, NMR analyses and computational studies are reported
Short peptides containing Norbornene amino acid (NRB): role of the NRB scaffold in self-assembly
No full textA number of papers report on spontaneous assembly of peptides into ordered nanostructures with a variety of morphologies and this number is still expanding.[1] Besides the numerous advantages of using peptides as building blocks for different types of nanostructures, some limitations are well-known such as a low stability in biological medium and their unstable conformation especially when they are short or medium-sized. The insertion of unnatural amino acids in the peptide sequences is a well-known tool to overcome these problems. Both theoretical and experimental studies on this subject have been published and, in particular, the group of Cα,-tetrasubstituted residues, in which the quaternary α-carbon is part of a ring has been the object of extensive investigation.[2] Notwithstanding this interest, studies on the self-assembly of short peptides containing cyclic Cα-tetrasubstituted amino acids are very rare.[3] The two diastereoisomeric pentapeptides AcAla-NRB-Ala-Aib-AlaNH2 1 and 2, containing the two enantiomers of the non-proteinogenic Cα-tetrasubstituted norbornene amino acid (NRB), were synthesized and their conformational analysis was performed. Interestingly, despite they are made of hydrophobic amino acids, they resulted insoluble in organic solvent, but completely soluble in water. The formation of supramolecular assemblies in water was assessed by TEM and DLS. Moreover, the stability of the aggregates in fetal bovine serum was evaluated and tested by DLS. A comparison between NRB containing peptides and other peptides containing cyclic and non-cyclic Cα-tetrasubstituted residues (i.e. Aib, Ac5AA) was done in order to better understand the role played by the NRB residue in aggregation phenomena
Peptidomimetics based on electrospun nanofibers
No full textElectrospinning is a simple and versatile technique used for the fabrication of continuous micro and nanofibers. This approach is inexpensive, scalable, reliable and mainly used from polymer solutions and polymer melts.
Recent studies have demonstrated that high molar mass polymers are not essential for production of uniform electrospun fibers but that sufficient intermolecular interactions acting as chain entanglements is the primary criterion.
A study on the electrospinnability of short peptide chains containing natural amino acids (Gly, Ala, Leu, Val) together with a heterocyclic scaffold properly functionalized, is here reported
Nanofibers from small molecules
No full textElectrospinning is a simple and versatile technique used for the fabrication of continuous micro and nanofibers. This approach is inexpensive, scalable, reliable and mainly used from polymer solutions and polymer melts.
Recent studies have demonstrated that high molar mass polymers are not essential for production of uniform electrospun fibers but that sufficient intermolecular interactions acting as chain entanglements is the primary criterion.[2]
A study on the electrospinnability of non natural small molecules is here reported for the first time
Nanoassemblies formed by ultrashort peptides for the vehiculation of hydrophobic molecules
No full textOver the last several decades, many papers report on spontaneous supramolecular assembly into ordered nanostructures with a variety of morphologies and this number is still expanding1. Among self-assembled supramolecules, peptides have attracted a great attention for biological applications due to their versatility and interesting chemical properties. In particular, our group is focused on the study of self-assembly of ultrashort peptides containing Cα-tetrasubstituted amino acids that are able to form soluble supramolecular structures in water, despite their hydrophobic nature2.
Here we present a short alanine (Ala), α-aminoisobutyric acid (Aib) based pentapeptide (Figure 1) that self-assemble into nanostructure having a spherical shape and a diameter around 300-400 nm (DLS results). These nanoassemblies could be exploited to vehiculate in an aqueous environment hydrophobic molecules, using encapsulation approach. As a proof of concept, we selected Curcumin, a polyphenol isolated from the rhizome of Curcuma longa. Curcumin is a fluorescent polyphenol with antioxidant, anti-inflammatory and anti-tumorigenic properties. On the other hand, it shows a very poor bioavailability in vivo, due to its low aqueous solubility and instability, rapid metabolism, and clearance, that definitely limits its use both as a nutraceutical and as a drug.
Fluorescence studies on curcumin loaded nanoaggregates show that the molecular interactions between Curcumin and the pentapeptide induce a blue shift and a change in the shape of the emission and absorption peaks of the fluorophore. The nature of these interactions is further being investigated with different techniques in order to demonstrate and explain the encapsulation process of hydrophobic molecules
Nanofibers from small molecules
No full textElectrospinning is a simple and versatile technique used for the fabrication of continuous micro and nanofibers. This approach is inexpensive, scalable, reliable and mainly used from polymer solutions and polymer melts.
Recent studies have demonstrated that high molar mass polymers are not essential for production of uniform electrospun fibers but that sufficient intermolecular interactions acting as chain entanglements is the primary criterion.
A study on the electrospinnability of non natural small molecules is here reported for the first time
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
- …
