Biospecific Interaction Analysis (BIA) as a Tool for the Design and Development of Gene Transcription Modifiers

Roberto      Gambari

Abstract

The applications of surface plasmon resonance (SPR) and biosensor technology for biospecific interaction analysis (BIA) of molecular interactions between transcription modifiers and target biomolecules is here described for the identification of possible candidates for drug research and development in antitumor and antiviral therapy. SPR-based BIA offers many advantages with respect to most of the other available methodologies to study biomolecular interactions. It should be underlined that (a) most commercially available biosensors are fully automated instruments; (b) no labelling is required; (c) a large variety of activated sensor chips are commercially available allowing the immobilization of either proteins or target DNA or RNA; (d) the amount of both ligand and analyte needed to obtain informative results is low; (e) the assay is rapid and (f) the sensor chip could be re-used many times, leading to low running costs, with the only limitation of verifying the stability of the immobilized ligand. Approaches employing SPR-based BIA were described for the development of (a) triple-helix forming oligonucleotides (TFO) and peptide nucleic acids (PNAs), (b) DNA-binding drugs, (c) decoy molecules and (d) PNAs able to perform strand invasion. All these biomolecules are of great interest for the development of transcription modifiers. Since alteration of the expression of transcription factors is involved in tumor cell growth and metastasis, SPR-based BIA appears to be a methodology of great impact in the design and development of anti-cancer agents.

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