Radio frequency gradient enhanced diffusion-edited semi-solid state NMR spectroscopy for detailed structural characterization of chemically modified hyaluronic acid hydrogels.

Applications of functionalized hyaluronic acid (HA) hydrogels for numerous biomedical applications requires their detailed structural characterization. Since these materials are prepared by multistep chemical modifications in the solid phase and not amenable to characterization by standard analytical tools, we employed high-resolution solid-state NMR spectroscopy to gain detailed insights into the structures of the functionalized HA hydrogels. Divinyl sulfone crosslinked HA hydrogels were converted into maleimide-functionalized hydrogels, which were subjected to chemoselective thiol-maleimide reaction using L-cysteine as the protein mimetic thiol reagent.

From laboratory to pilot plant: the solid-state process development of a highly potent cathepsin S/K inhibitor.

The solid-state development for the low dose drug molecule SAR114137, a selective and reversible inhibitor of cysteine cathepsin S/K, is reported. Six polymorphic forms as well as various solvate phases were discovered by an extensive polymorphism screening. The solid phase characterizations revealed that phase 1, from which a single crystal structure could be obtained, is the thermodynamically most stable form and therefore it was chosen for pharmaceutical development.

Novel β-amino acid derivatives as inhibitors of cathepsin A.

Cathepsin A (CatA) is a serine carboxypeptidase distributed between lysosomes, cell membrane, and extracellular space. Several peptide hormones including bradykinin and angiotensin I have been described as substrates. Therefore, the inhibition of CatA has the potential for beneficial effects in cardiovascular diseases.

Organosilicon-mediated total synthesis of the triquinane sesquiterpenes (±)-β-isocomene and (±)-isocomene.

We describe an efficient total synthesis of the sesquiterpenes (±)-β-isocomene and (±)-isocomene using a Lewis acid-promoted [3 + 2] cycloaddition of allyl-tert-butyldiphenylsilane as the key-step.