Síntesis de antígenos dendrimericos aplicados al estudio de reacciones alérgicas a medicamentos

Resumen

A pharmaceutical drug is any chemical substance intended for use in the medical diagnosis, cure, treatment or prevention of disease. As any substance that is capable of producing a therapeutic effect, it can also produce unwanted or adverse effects. Hypersensitivity reactions result from the immune system responding in an appropriate manner to an inappropriate stimulus. Immediate hypersensitivity reactions are mediated by immunoglobulin E (IgE). Of the in vitro methods currently available, immunoassays for the detection of drug-specific IgE antibodies are the most widely used. Immunoassays are based on detection of antigen (hapten-carrier conjugate) and IgE antibody binding. The principal condition for immunoassays is that the hapten molecule or drug must be bound to a carrier molecule. A new kind of dendrimer was synthesized, called BAPAD, based on repetitive amide bonds of 3,3¿-diaminpivalamide moieties by a repeated method of amide bond formation with 3,3¿-diazidopivalic acid and reduction of azide groups to amine groups. This method was put into practice until the third generation of dendrons and dendrimers and it was protected with a patent. Furthermore, haptenized-BAPAD with AXO units were synthesized and assayed in RAST inhibition studies letting us check that inhibition occurred, so recognition existed between IgE and BAPAD-AXO structures. Hapten-dendrimer (BPO-PAMAM) functionalized zeolite L were successfully fabricated, characterized and validated as solid phases in RAST assay. A scalable collection of oligoethylene glycol chains ranging from di- to pentaethylene glycol, which possessed two different, orthogonally functional groups at their chain ends, could be directly synthesized and obtained with no tedious workup simply by treating their corresponding aromatic-functionalized symmetric dialdehydes under conventional Cannizzaro conditions. The use of a desymetrizated glycol chain as linker to bind hapten-dendrimer (AXO-PAMAM) to the surface of a sensor of SPR was assayed. The introduction of a moiety of 1,8-naphthalimide in a haptenized dendron structure bound over the surface of cellulose disks allowed a characterization of solid supports for RAST assays, having a new property, fluorescence, to measure the haptenization degree and the reproducibility, and providing also an effective control on the manufacture of the cellulose disks for RAST assays.