Effect of Steric Constraint at the γ-Backbone Position on the Conformations and Hybridization Properties of PNAs

Conformationally preorganized peptide nucleic acids (PNAs) have been synthesized through backbone modifications at the γ-position, where R = alanine, valine, isoleucine, and phenylalanine side chains. The effects of these side-chains on the conformations and hybridization properties of PNAs were determined using a combination of CD and UV-Vis spectroscopic techniques. Our results show that the γ-position can accommodate varying degrees of sterically hindered side-chains, reaffirming the bimodal function of PNAs as the true hybrids of “peptides” and “nucleic acids.

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Conformationally preorganized peptide nucleic acids (PNAs) have been synthesized through backbone modifications at the γ-position, where R = alanine, valine, isoleucine, and phenylalanine side chains. The effects of these side-chains on the conformations and hybridization properties of PNAs were determined using a combination of CD and UV-Vis spectroscopic techniques. Our results show that the γ-position can accommodate varying degrees of sterically hindered side-chains, reaffirming the bimodal function of PNAs as the true hybrids of "peptides" and "nucleic acids.&quot

Surface properties of distinct nanofibrillated celluloses assessed by inverse gas chromatography

The adhesion and surface properties of nanocelluloses are an important issue to consider when using this material for composites production, in food packaging or coatings, as well as for determining the influence of added functional groups. In the present work, the surface properties of two nanofibrillated celluloses obtained by mild 2,2,6,6-tetramethylpiperidine-1- oxyl radical (TEMPO)-mediated oxidation with distinct mechanical treatment intensity in a homogenizer (5 and 15 passes), and one nanofibrillated cellulose obtained by enzymatic process, were thoroughly assessed by inverse chromatography, at infinite dilution conditions. The dispersion component of the surface energy ( s d) was 42-46 mJ m-2 at 40 ºC for the TEMPO nanofibres and 52 mJ m-2 for the enzymatic nanocellulose. It was confirmed, based on the determination of the specific components of the works of adhesion and enthalpies of adsorption with polar probes, that the surfaces of the materials have a more Lewis acidic than Lewis basic character. Regarding TEMPO nanofibres, a slight increase of Lewis acidity/basicity ratio seemed to occur for the more nanofibrillated material (15-passes). Higher specific interactions with polar probes were found for enzymatic nanocellulose. The higher values of s d and specific interactions observed for the enzymatic nanocellulose could partly be due to the higher crystallinity of this sample. On the other hand, the increase of the acidity/basicity ratio (as well as of the s d value) for the 15-passes vs. 5-passes TEMPO nanofibres was attributed to a higher exposition of the hydroxyl groups of cellulose at the surface of the former material

A colorimetric strategy based on dynamic chemistry for direct detection of Trypanosomatid species

Leishmaniasis and Chagas disease are endemic in many countries, and re-emerging in the developed countries. A rapid and accurate diagnosis is important for early treatment for reducing the duration of infection as well as for preventing further potential health complications. In this work, we have developed a novel colorimetric molecular assay that integrates nucleic acid analysis by dynamic chemistry (ChemNAT) with reverse dot-blot hybridization in an array format for a rapid and easy discrimination of Leishmania major and Trypanosoma cruzi. The assay consists of a singleplex PCR step that amplifies a highly homologous DNA sequence which encodes for the RNA component of the large ribosome subunit. The amplicons of the two different parasites differ between them by single nucleotide variations, known as “Single Nucleotide Fingerprint” (SNF) markers. The SNF markers can be easily identified by naked eye using a novel micro Spin-Tube device "Spin-Tube", as each of them creates a specific spot pattern. Moreover, the direct use of ribosomal RNA without requiring the PCR pre-amplification step is also feasible, further increasing the simplicity of the assay. The molecular assay delivers sensitivity capable of identifying up to 8.7 copies per μL with single mismatch specificity. The Spin-Tube thus represents an innovative solution providing benefits in terms of time, cost, and simplicity, all of which are crucial for the diagnosis of infectious disease in developing countries.This research work has received funding from Junta de Andalucía, Consejería de Economía e Innovación (project number 2012-BIO1778), the Spanish Ministerio de Economía y Competitividad (Grants CTQ2012-34778, BIO2016-80519-R, FPI Grant BES-2013- 063020). This research was partially supported by the 7th European Community Framework Program (FP7-PEOPLE-2012-CIG-Project Number 322276)

Synthesis and characterization of conformationally preorganized, (R)-diethylene glycol-containing γ-peptide nucleic acids with superior hybridization properties and water solubility.

Developed in the early 1990s, peptide nucleic acid (PNA) has emerged as a promising class of nucleic acid mimic because of its strong binding affinity and sequence selectivity toward DNA and RNA and resistance to enzymatic degradation by proteases and nucleases; however, the main drawbacks, as compared to other classes of oligonucleotides, are water solubility and biocompatibility. Herein we show that installation of a relatively small, hydrophilic (R)-diethylene glycol ("miniPEG", R-MP) unit at the γ-backbone transforms a randomly folded PNA into a right-handed helix. Synthesis of optically pure (R-MP)γPNA monomers is described, which can be accomplished in a few simple steps from a commercially available and relatively cheap Boc-l-serine. Once synthesized, (R-MP)γPNA oligomers are preorganized into a right-handed helix, hybridize to DNA and RNA with greater affinity and sequence selectivity, and are more water soluble and less aggregating than the parental PNA oligomers. The results presented herein have important implications for the future design and application of PNA in biology, biotechnology, and medicine, as well as in other disciplines, including drug discovery and molecular engineering.</p