Towards combining backbone and sugar constraint in 3'-3' bis-phosphonate tethered 2'-4' bridged LNA oligonucleotide trimers.

Therapeutic oligonucleotides are chemically modified to enhance their drug-like properties - including binding affinity for target RNA. Many nucleic acid analogs that enhance RNA binding affinity constrain the furanose sugar in an RNA-like sugar pucker. The improvements in binding affinity result primarily from increased off-rates with minimal effects on on-rates for hybridization.

Structure-activity relationships of N-terminal variants of peptidomimetic tissue transglutaminase inhibitors.

Tissue transglutaminase (TG2) is a multifunctional protein that catalyses protein crosslinking in the extracellular matrix, and functions as an intracellular G-protein. While both activities have been associated with human diseases, its role as a G-protein has been linked to cancer stem cell survival and maintenance of a metastatic phenotype. Recently we have shown that targeted covalent inhibitors (TCIs) can react selectively with the enzyme active site of TG2, to allosterically abolish its ability to bind GTP.

A Novel, Fast and Efficient One-Pot Three-Component Procedure for the Preparation of New Imidazolidinone Derivatives from Isocyanide, Aldehyde and Urea.

Background: Multicomponent processes have played powerful roles in achieving complex structures, which are also aligned with green chemistry. Thus, MCRs have attracted considerable interest due to their atom economy, simple experimental procedures, automated synthesis, convenience and synthetic efficiency. Isocyanides are one of the crucial starting material in designing MCRs methods.

Palladium Catalyzed, Multicomponent Synthesis of Fused-Ring Pyrroles from Aryl Iodides, Carbon Monoxide, and Alkyne-Tethered Imines.

A palladium-catalyzed multicomponent route to polycyclic pyrroles is described. Pd(PBu) was found to catalyze the coupling of (hetero)aryl iodides, two equivalents of carbon monoxide and alkyne-tethered imines into 1,3-dipoles (Münchnones), which undergo spontaneous, intramolecular 1,3-dipolar cycloaddition to form polycyclic pyrroles. The systematic variation of the alkyne, tethered-imine, or aryl iodide can allow the buildup of a range of pyrrole derivatives, where any of the substituents can be independently varied.