Hybrid systems for oral delivery of a therapeutic neuropeptide

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The statistical significance of selected sense–antisense peptide interactions

Sense and antisense peptides, encoded by sense and corresponding antisense DNA strands, are capable of specific interactions that could be a driving force to mediate protein–protein or protein–peptide binding associations. The complementary residue hypothesis suggests that these interactions are founded upon the sum of pairwise interactions between amino acids encoded by corresponding sense and antisense codons. Despite many successful experimental results obtained with the hypothesis, however, the physicochemical basis for these interactions is poorly understood. We examined the potential of the hypothesis for general identification of protein–protein interaction sites, and the possible role of the hypothesis in determining folding in a broad set of protein structures. In addition, we performed a structural study to investigate the binding of a complementary peptide to IL‐1F2. Our results suggest that complementary residue pairs are no more frequent or conserved than average in protein–protein interfaces, and are statistically under‐represented amongst contacting residue pairs in folded protein structures. Although our structural results matched experimental observations of binding between the peptide and IL‐1F2, complementary residue interactions do not appear to be dominant in the bound structure. Overall, our data do not allow us to conclude that the complementary residue hypothesis accounts for specific sense–antisense peptide interactions. © 2012 Wiley Periodicals, Inc.     

Synthesis and anticancer properties of RGD peptides conjugated to nitric oxide releasing functional groups and abiraterone

A series of analogues of the integrin binding aspartic acid-glycine-arginine (RGD) peptide sequence were synthesised conjugated to nitric oxide (NO) donating functional groups. Also the cytotoxicity of abiraterone, a prostate cancer drug, was explored when it was conjugated in three part constructs to RGD sequences and NO releasing heterocycles. In general the analogues showed integrin binding affinity comparable to RGD reference compounds, and all released NO by the Griess test assay. Two analogues exhibited significant cytotoxic effects against PC3 and MCF7 cell lines.     

Extended Peptide Nucleic Acid Nucleobases Based on Isoorotic Acid for the Recognition of A–U Base Pairs in Double-Stranded RNA

Peptide nucleic acids (PNA) with extended isoorotamide containing nucleobases ( I _o ) were designed for binding A–U base pairs in double-stranded RNA. Isothermal titration calorimetry and UV thermal melting experiments revealed improved affinity for A–U using the Io scaffold in PNA. PNAs having four sequential Io extended nucleobases maintained high binding affinity.     

Copper nanoclusters as peroxidase mimetics and their applications to H2O2 and glucose detection

Copper nanoclusters (Cu NCs) are found to possess intrinsic peroxidase-like activity for the first time. Similar to nature peroxidase, they can catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine by H₂O₂ to produce a nice blue color reaction. Compared with horseradish peroxidase, Cu NCs exhibits higher activity near neutral pH, which is beneficial for biological applications. The increase in absorbance caused by the Cu NCs catalytic reaction allows the detection of H₂O₂ in the range of 10 μM to 1 mM with a detection limit of 10 μM. A colorimetric method for glucose detection was also developed by combining the Cu NCs catalytic reaction and the enzymatic oxidation of glucose with glucose oxidase. Taking into account the advantages of ultra-small size, good stability, and high biocompatibility in aqueous solutions, Cu NCs are expected to have potential applications in biotechnology and clinical diagnosis as enzymatic mimics.     

Disposable amperometric magnetoimmunosensor for the sensitive detection of the cardiac biomarker amino-terminal pro-B-type natriuretic peptide in human serum

A novel amperometric magnetoimmunosensor using an indirect competitive format is developed for the sensitive detection of the amino-terminal pro-B-type natriuretic peptide (NT-proBNP). The immunosensor design involves the covalent immobilization of the antigen onto carboxylic-modified magnetic beads (HOOC-MBs) activated with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC) and N-hydroxysulfosuccinimide (sulfo-NHS), and further incubation in a mixture solution containing variable concentrations of the antigen and a fixed concentration of an HRP-labeled detection antibody. Accordingly, the target NT-proBNP in the sample and that immobilized on the MBs compete for binding to a fixed amount of the specific HRP-labeled secondary antibody. The immunoconjugate-bearing MBs are captured by a magnet placed under the surface of a disposable gold screen-printed electrode (Au/SPE). The amperometric responses measured at –0.10 V (vs. a Ag pseudo-reference electrode), upon addition of 3,3′,5,5′-tetramethylbenzidine (TMB) as electron transfer mediator and H₂O₂ as the enzyme substrate, are used to monitor the affinity reaction. The developed magnetoimmunosensor provides attractive analytical characteristics in 10-times diluted human serum samples, exhibiting a linear range of clinical usefulness (0.12–42.9 ng mL⁻¹) and a detection limit of 0.02 ng mL⁻¹, which can be used in clinical diagnosis of chronic heart failure in the elderly and for classifying patients at risk of death after heart transplantation. The magnetoimmunosensor was successfully applied to the analysis of spiked human serum samples.