(1810 - 1896)
Zoólogo alemán. Su labor científica fue enorme en el campo de las investigaciones zoológicas. Sus aportes se plasmaron en obras sobre mamíferos, aves, insectos, reptiles y moluscos.
Biomedical Sciences
1997 | Introduction of exposition technology of proteins in bacteriophages’ surface to characterize Protein-Protein Interaction and the design of new molecules
Main author: Nelson Santiago Vispo
Summary: This work includes the use of TEPF in: producing IL-2 as biologically active and secreted protein in E. coli, obtaining mutants’ library of IL-2, and characterizing the epitopes recognized by monoclonal antibodies in their respective ligands. In the last case, its application allowed corroborating structural predictions and selecting potential peptic agonists/antagonists of their ligands.This is the first report of how filamentous phages are able to expose human Interleukin-2 fused to protein III, from the design and construction of a new secretion peptide in E. coli. The IL2 exposed in the phage si biologically active; this find allowed the construction of a mutants’ library of IL-2 to select molecule’s agonists and antagonists, potentially useful in the prophylaxis and therapy of organs’ transplant, the autoimmune diseases and the control of leukemic growth.CB IL2-1 monoclonal antibody specific for IL-2 has neutralizing activity in trials of cellular proliferation of CTLL-2 murine line. It has also been used in a transplant rejection module in rats, where it works as antagonist of IL-2 system. With the use of TEPF, it was possible locating the specific zone inside IL-2 molecule that recognizes this antibody, which is between the aminoacids L72 and L80. The zone is spatially related to the union site to IL-2 receptor, hence the neutralizing character of this antibody.It was also identified the aminoacid region in IL2 molecule recognized by CB-IL2.2 monoclonal antibody; these aminoacids are a part of a bound between T101 and M104. As there were not reported data on crystallography of this bond, it was built a three-dimensional model, where the epitope is favorably exposed in the protein’s surface. The peptides’ exposition methodology is presented in this result with a great predictive value, which validates the theoretical three-dimensional model of this fragment of the IL-2.In the case of CB-Hep1 monoclonal antibody, it was possible to define the CKTC region of the "a" determinant, critic for its "common" character, which guarantees that during immunopurification those antigen molecules are selected to expose this region appropriately, essential for the development of an immune protector response facing different viral subtypes. From the technological point of view, it was established for the first time in our country a methodology for the exhibition of proteins and heterologous peptides in the surface of filamentous fages. The system is very applicable in the world arena, in the design of new molecules of therapeutic or diagnostic use, and in the improvement of existent recombinant products.