Antibody-mimicking proteins created that could be used to design more effective drugs
The advance represents a development of more accessible drugs on a global scale and enables new mechanisms of action
Researchers from the Higher Council for Scientific Research (CSIC) and the Institute for Protein Design have co-designed and created new proteins, non-existent in nature, with structures that imitate immunoglobulins of antibodies, which are the proteins used by the immune system to identify and neutralize foreign bodies such as pathogenic bacteria and viruses.< /p>
The work, published in 'Nature Communications', opens the door to the development of drugs based on monoclonal antibodies tailored and more affordable, whose applications range from cancer to autoimmune diseases and viral infections.
This study describes a computational strategy to design “small immunoglobulins (proteins) such as those of antibodies with tailored structures, high stability and with the ability to anchor flexible zones with the ability to bind to the desired target”, explains Enrique Marcos, co-director of the study together with F. Xavier Gomis Rüth , both from the Institute of Molecular Biology of Barcelona (IBMB-CSIC), and together with David Baker, from the Institute for Protein Design of the University of Washington (USA).
The part of the antibodies that is modified is a very specific one. “The structure of all antibodies is very similar, but at their ends they differ in a small variable region that is what allows each antibody to specifically recognize a target“, explains Marcos.
This variable region is a structural framework with folded immunoglobulins, a framework in which a flexible zone is anchored that interacts and directly recognizes the pathogen< /strong>.
Using this strategy, scientists They have generated the new molecules (proteins) and then they have verified by means of crystallography that the structures obtained were those predicted in the models, which means that they can design them with high precision. n.
Objective: effective drugs
The work, in which teams from the University of Toronto have also participated, opens the door to design of antibody-like proteins with structures adapted to the needs and that have better biophysical properties than the current ones. so Therefore, this would represent a great advance for the development of more accessible drugs on a global scale and enabling new mechanisms of action.
Drugs based on monoclonal antibodies consist of modifying a part of the antibodiesso that they are able to recognize therapeutic targets and attack specific cells.
These are the most promising drugs and the most advanced in the pharmaceutical industry >, especially for the treatment of different types of cancer, autoimmune diseases and, more recently, viral infections.
However, they point out, “these are therapies still very expensiveand there are limitations that slow down their progress, such as their low stability, their large size and difficult large-scale production, among others.”
That is why they are highly They are costly to develop, produce and, being very unstable, also difficult to distribute, as they require adequate storage and refrigeration conditions.This new study using computational design could contribute to achieve more precise, stable and affordable drugs.
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