New Biosensor for Determination of Neuropilin-1 with Detection by Surface Plasmon Resonance Imaging

Neuropilin-1 is transmembrane protein with soluble isoforms. It plays a pivotal role in both physiological and pathological processes. NRP-1 is involved in the immune response, formation of neuronal circuits, angiogenesis, survival and migration of cells. The specific SPRI biosensor for the determination of neuropilin-1 was constructed using mouse monoclonal antibody that captures unbound NRP-1 form body fluids. The biosensor exhibits linearity of the analytical signal between 0.01 and 2.5 ng/mL, average precision value 4.7% and recovery between 97% and 104%. The detection limit is 0.011 ng/mL, and the limit of quantification is 0.038 ng/mL. The biosensor was validated by parallel determination of NRP-1 in serum and saliva samples using the ELISA test, with good agreement of the results

General Synthesis of Unsymmetrical 3,3′-(Aza)diindolylmethane Derivatives

Diindolylmethane (DIM) and its derivatives have recently been in the focus of interest due to their significant biological activities, specifically in cancer prevention and therapy. Molecular targets of DIM have been identified, e.g., the immunostimulatory G protein-coupled receptor GPR84. However, most of the reported and investigated DIM derivatives are symmetrical because general methods for obtaining unsymmetrical DIMs have been lacking. To optimize the interaction of DIM derivatives with their protein targets, unsymmetrical substitution is required. In the present study we developed a new, mild and efficient access to unsymmetrically substituted 3,3′-DIMs by reaction of (3-indolylmethyl)­trimethylammonium iodides with a wide range of substituted indole derivatives. 7-Azaindole also led to the 3,3′-connected DIM analogue, while 4- and 5-azaindoles reacted at the <i>N</i>1-nitrogen atom as confirmed by X-ray crystallography. The reactions were performed in water without the requirement of a catalyst or other additives. Wide substrate scope, operational simplicity, environmentally benign workup, and high yields are further advantages of the new method. The synthetic protocol proved to be suitable for upscaling to yield gram amounts for pharmacological studies. This procedure will allow the preparation of a broad range of novel, unsymmetrical DIM derivatives to exploit their potential as novel drugs