Synthetic Peptide Antibodies as TNF-α Inhibitors: Molecularly Imprinted Polymer Nanogels Neutralize the Inflammatory Activity of TNF-α in THP-1 Derived Macrophages

Tumor Necrosis Factor-α (TNF-α) is a cytokine that is normally produced by immune cells when fighting an infection. But, when too much TNF-α is produced as in autoimmune diseases, this leads to unwanted and persistent inflammation. Anti-TNF-α monoclonal antibodies have revolutionized the therapy of these disorders by blocking TNF-α and preventing its binding to TNF-α receptors, thus suppressing the inflammation. Herein, we propose an alternative in the form of molecularly imprinted polymer nanogels (MIP-NGs). MIP-NGs are synthetic antibodies obtained by nanomoulding the 3-dimensional shape and chemical functionalities of a desired target in a synthetic polymer. Using an in-house developed in silico rational approach, epitope peptides of TNF-α were generated and ‘synthetic peptide antibodies’ were prepared. The resultant MIP-NGs bind the template peptide and recombinant TNF-α with high affinity and selectivity, and can block the binding of TNF-α to its receptor. Consequently they were applied to neutralize pro-inflammatory TNF-α in the supernatant of human THP-1 macrophages, leading to a downregulation of the secretion of pro-inflammatory cytokines. Our results suggest that MIP-NGs, which are thermally and biochemically more stable and easier to manufacture than antibodies, and cost-effective, are very promising as next generation TNF-α inhibitors for the treatment of inflammatory diseases.     

Two-step oxidative one pot functionalization of 2-benzylidene-1-tetralone in the PdII/CuII/Na2CO3-MeOH system: a novel route to 2-(α-methoxy)benzyl-1,4-naphthoquinone

A novel two-step oxidative one pot functionalization of 2-benzylidene-1-tetralone by its reaction with Na₂PdCl₄ in the presence of CuCl₂ and Na₂CO₃ (in 1 1 2 5 molar ratio) in MeOH was discovered. The reaction yields 2-(-methoxy)benzyl-1,4-naphthoquinone.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 986–988, May, 1995.This work was carried out with the financial support of the Russian Foundation for Basic Research (Project No. 94-03-08873) and the International Science Foundation (Grant MHW 000).