Synthesis and biological evaluation of 3,5-diaminoindazoles as cyclin-dependent kinase inhibitors.

A novel series of 3,5-diaminoindazoles were prepared and found to be CDK inhibitors. Potent inhibitors against CDK1 and CDK2 were obtained by introduction of 1lambda(6)-isothiazolidine-1,1-dioxide at 5-position of indazole. Anti-proliferative activities of compounds were evaluated using EJ, HCT116, SW620, and A549 cancer cell lines.

Protein-directed immobilization of phosphocholine ligands on a gold surface for multivalent C-reactive protein binding.

The preparation of a synthetic receptor for multivalent protein binding by a directed immobilization of bifunctional ligands was demonstrated using pentameric C-reactive protein (CRP) and a thiolated phosphocholine-containing ligand on a gold surface. CRP consisting of five identical, noncovalently linked subunits and having five phosphocholine-binding sites on the same face was complexed with 12-mercaptododecylphosphocholine. The complexes were reacted with a gold surface, which was blocked with BSA or 2-mercaptoethanol to avoid non-specific binding. CRP binding to the molecularly imprinted monolayer was investigated by surface plasmon resonance, exhibiting high sensitivity with a detection limit as low as 1 pM (0.12 ng/mL) and binding affinity (K(A) ~ 10(-7)-10(-9) M(-1)) comparable to that of immobilized anti- CRP.

C-Reactive protein-directed immobilization of phosphocholine ligands on a solid surface.

The complexes of C-reactive protein (CRP) with its polymerizable phosphocholine ligands adsorbed at the styrene-water interface were polymerized. The molecularly imprinted polymer (MIP) exhibited a binding affinity for CRP comparable to that of immobilized anti-CRP antibody. The determination of human serum CRP using the MIP-based sandwich immunoassay has been demonstrated.