Combination of the 2A/furin technology with an animal component free cell line development platform process.

The recently described 2A/furin technology combines both chains of the antibody in a single open reading frame. Upon translation and secretion, the peptide is processed by the cell to generate native fully functional IgG antibodies. Here, we describe the results of an evaluation study of this technology for an industrial CHO cell line development process.

Sensitivity enhancement in saturation transfer difference (STD) experiments through optimized excitation schemes.

Investigation of ligand-protein interactions by the saturation transfer difference (STD) experiment has been well established in the drug discovery process through numerous examples. Thus, binding epitopes may be mapped by comparing signals of the ligand with and without saturation of the protein. Herein, it is shown that a less selective process allows more protons to assist in the saturation of the protein, thereby considerably enhancing the sensitivity of the STD experiment.

CRIT is expressed on podocytes in normal human kidney and upregulated in membranous nephropathy.

Complement C2 receptor inhibitor trispanning (CRIT) is a novel human complement regulatory cell surface receptor. It binds the human complement protein C2 and blocks the classical pathway of complement activation, thus protecting the cell against complement attack. CRIT expression in the kidney was analyzed by immunohistochemistry and in situ hybridization.

(-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism of action, and neuroprotection.

Group-III metabotropic glutamate receptors (mGluR4, -6, -7, and -8) modulate neurotoxicity of excitatory amino acids and beta-amyloid-peptide (betaAP), as well as epileptic convulsions, most likely via presynaptic inhibition of glutamatergic neurotransmission. Due to the lack of subtype-selective ligands for group-III receptors, we previously utilized knock-out mice to identify mGluR4 as the primary receptor mediating neuroprotection of unselective group-III agonists such as L-AP(4) or (+)-PPG, whereas mGluR7 is critical for anticonvulsive effects. In a recent effort to find group-III subtype-selective drugs we identified (+/-)-PHCCC as a positive allosteric modulator for mGluR4.

(+)-4-phosphonophenylglycine (PPG) a new group III selective metabotropic glutamate receptor agonist.

A new synthesis of (R,S)-PPG (4-phosphonophenylglycine) and the separation of the protected enantiomers leading after deprotection to (+)- and (-)-PPG are described. Pharmacological characterization at the group III metabotropic glutamate receptors hmGluR4a and hmGluR7b revealed (+)-PPG as the active enantiomer.