The advance represents a development of more accessible drugs on a global scale and enabling 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 proteinsnon-existent in nature, with structures that mimic the immunoglobulins of antibodieswhich are proteins used by the immune system to identify and neutralize bodies strangers such as pathogenic bacteria and viruses.
The work, published in ‘Nature Communications’, opens the door to development of drugs based on monoclonal antibodies tailored and more affordable, with applications ranging from cancer to autoimmune diseases and viral infections.
This study describes a computational strategy for 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 of 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. “The structure of all antibodies is very similar, but at their ends they differ in a small variable region that allows each antibody specifically recognizes a targetMark explains.
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.
With this strategy, scientists have generated 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.
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 con structures adapted to the needs and that they present better biophysical properties than the current ones. Thus, this would represent a great breakthrough for drug development more accessible on a global scale and enabling new mechanisms of action.
Monoclonal antibody-based drugs consist of modify a part of the antibodies so that they are able to recognize therapeutic targets and attack specific cells.
These are the most promising drugs and most advanced in the pharmaceutical industryespecially for the treatment of different types of cancer, autoimmune diseases and, more recently, viral infections.
However, they point out, “they are therapies still very expensive and there are limitations that slow down its progress, such as its low stability, its large size and difficult large-scale production, among others”.
That’s why they are highly expensive drugs to develop, produce and, being very unstable, also difficult to distribute, since they require adequate storage and refrigeration conditions. This new study using computational design could contribute to achieving more precise, stable and affordable drugs.