Targeting apoptosis via chemical design: inhibition of bid-induced cell death by small organic molecules

Bid is a key member of the Bcl-2 family proteins involved in the control of the apoptotic cascade in cells, leading to cell death. Uncontrolled cell death is associated with several human pathologies, such as neurodegenerative diseases and ischemic injuries. Therefore, Bid represents a potential yet unexplored and challenging target for strategies aimed at the development of therapeutic agents. Here we show that a multidisciplinary NMR-based approach that we named SAR by ILOEs (structure activity relationships by interligand nuclear Overhauser effect) allowed us to rationally design a series of 4-phenylsulfanyl-phenylamine derivatives that are capable of occupying a deep hydrophobic crevice on the surface of Bid. These compounds represent the first antiapoptotic small molecules targeting a Bcl-2 protein as shown by their ability to inhibit tBid-induced SMAC release, caspase-3 activation, and cell death.     

Mechanism of Formation of Peroxocarbonates RhOOC(O)O(Cl)(P)(3) and Their Reactivity as Oxygen Transfer Agents Mimicking Monooxygenases. The First Evidence of CO(2) Insertion into the O-O Bond of Rh(eta(2)-O(2)) Complexes

Extended labeling experiments have shown that formation of rhodium peroxocarbonate from CO(2) and [RhCl(eta(2)-O(2))(P)(3)] (P is PEt(2)Ph or PEtPh(2)) proceeds through O-O bond cleavage and CO(2) insertion. O-transfer to ancillary phosphine ligand to give R(3)P=O selectively (>85%) involves the Rh-linked O atom of the peroxo group of RhCl(CO(4))(P)(3).     

Chiral Fibers Formation Upon Assembly of Tetraphenylalanine Peptide Conjugated to a PNA Dimer

Self-assembly of biomolecules such as peptides, nucleic acids or their analogues affords supramolecular objects, exhibiting structures and physical properties dependent on the amino-acid or nucleobase composition. Conjugation of the peptide diphenylalanine (FF) to peptide nucleic acids triggers formation of self-assembled structures, mainly stabilized by interactions between FF. In this work we report formation of homogeneous chiral fibers upon self-assembly of the hybrid composed of the tetraphenylalanine peptide (4F) conjugated to the PNA dimer adenine-thymine (at). In this case nucleobases seem to play a key role in determining the morphology and chirality of the fibers. When the PNA “at” is replaced by guanine-cytosine dimer “gc”, disordered structures are observed. Spectroscopic characterization of the self-assembled hybrids, along with AFM and SEM studies is reported. Finally, a structural model consistent with the experimental evidence has also been obtained, showing how the building blocks of 4Fat arrange to give helical fibers.     

Determination of intraperitoneal mitoxantrone in the serum of cancer patients using a high performance liquid chromatograph coupled to an Advanced Automated Sample Processor (AASP).

A study has been carried out on 10 patients with ovarian cancer treated by intraperitoneal mitoxantrone. The serum concentration was determined by high performance liquid chromatography with spectrophotometric detection. The extracted analyte on the cartridge was injected and eluted on-line into the analytical column by the mobile phase. This improved the signal and sample processing rate, without significant loss in analytical performance. Excellent linearity (r greater than 0.9994) was observed for the calibration curve over the range 1-2000 ng/mL, along with a precision within-day and between-day estimated as 1.5% and 5.6%, respectively. Sensitivity was an order of magnitude higher than that of the comparison method. From a clinical point of view, these preliminary results have shown that intraperitoneal administration is more beneficial than intravenous therapy. Low serum levels (1-30 ng/mL) with a maximum at the first or second hour are revealed.     

Efficient electron transfer through a triazole link in ruthenium(II) polypyridine type complexes

Spectroscopic, electrochemical and theoretical characterisations of photoactive systems readily assembled via click-chemistry show an efficient bi-directional charge shift through the triazole link.