Solnatide is a synthetic peptide, which is in clinical trials to treat (life-threatening) lung failure in patients with Acute Respiratory Distress Syndrome (ARDS) and COVID-19.
In this project, the researchers detail the structure of solnatide and propose a mechanism of interaction with the ENaC sodium channel of cells, which is related to the volume of liquid in the cellular environment.
The work has been published in the Computational and Structural Biotechnology Journal.
Pulmonary edema is an abnormal accumulation of fluid in the lungs that results in shortness of breath, is life-threatening, and occurs in patients with acute respiratory distress syndrome and COVID-19. This accumulation of fluid causes a lack of oxygenation of the blood and is related to defects in the functioning of the sodium channels responsible for regulating water levels inside and outside the cells.
A collaboration led by Dr. Maria Macias, ICREA researcher and head of the Structural Characterization of Macromolecular Assemblies laboratory at IRB Barcelona, and Dr. Susan Tzotzos, from the Austrian biotech APEPTICO, has revealed the structure of solnatide, a molecule that is being being tested for the treatment of pulmonary edema. Specifically, this project has made it possible to detail the mechanism of interaction of sonatide with the ENaC sodium channel of the cell, responsible for the elimination of pulmonary fluid.
The APEPTICO company from Vienna (Austria), owner of solnatide, has been working with this molecule for many years, studying its biological function. At the moment, the molecule is in the clinical trial phase to treat pulmonary edema in patients with Acute Respiratory Distress Syndrome (ARDS), as well as severe COVID-19 patients with ARDS.
"Our work has focused on describing the structure of the peptide and proposing a mechanism of action to open the door to possible improvements in its sequence, that is, to small modifications that can make it more effective," explains Dr. Macías.
A helix and a dipole
The structure of the sodium channel in cells was already partially described, but there remained a less structured region that was not yet known. In this work, published in the Computational and Structural Biotechnology Journal, the researchers have used structure prediction tools including Alphafold, to identify a helical region aligned with the cell membrane, by the cytoplasmic part. That helix would have a positively charged region and a negatively charged region.
The solnatide, for its part, also had a region called a "dipole", with a negative and a positive charge. Thus, the researchers were able to predict that this would be the point of interaction between both structures and how they were positioned for that interaction.
Researchers from the Catalan biotech BCN Peptides in Barcelona (Spain), and from the American universities Medical College of Georgia at Augusta University and Emory University School of Medicine, in Atlanta, have also collaborated in the work.
Pulmonary edema is an abnormal accumulation of fluid in the lungs that results in shortness of breath, is life-threatening, and occurs in patients with acute respiratory distress syndrome and COVID-19. This accumulation of fluid causes a lack of oxygenation of the blood and is related to defects in the functioning of the sodium channels responsible for regulating water levels inside and outside the cells.
A collaboration led by Dr. Maria Macias, ICREA researcher and head of the Structural Characterization of Macromolecular Assemblies laboratory at IRB Barcelona, and Dr. Susan Tzotzos, from the Austrian biotech APEPTICO, has revealed the structure of solnatide, a molecule that is being being tested for the treatment of pulmonary edema. Specifically, this project has made it possible to detail the mechanism of interaction of sonatide with the ENaC sodium channel of the cell, responsible for the elimination of pulmonary fluid.
The APEPTICO company from Vienna (Austria), owner of solnatide, has been working with this molecule for many years, studying its biological function. At the moment, the molecule is in the clinical trial phase to treat pulmonary edema in patients with Acute Respiratory Distress Syndrome (ARDS), as well as severe COVID-19 patients with ARDS.
"Our work has focused on describing the structure of the peptide and proposing a mechanism of action to open the door to possible improvements in its sequence, that is, to small modifications that can make it more effective," explains Dr. Macías.
A helix and a dipole
The structure of the sodium channel in cells was already partially described, but there remained a less structured region that was not yet known. In this work, published in the Computational and Structural Biotechnology Journal, the researchers have used structure prediction tools including Alphafold, to identify a helical region aligned with the cell membrane, by the cytoplasmic part. That helix would have a positively charged region and a negatively charged region.
The solnatide, for its part, also had a region called a "dipole", with a negative and a positive charge. Thus, the researchers were able to predict that this would be the point of interaction between both structures and how they were positioned for that interaction.
Researchers from the Catalan biotech BCN Peptides in Barcelona (Spain), and from the American universities Medical College of Georgia at Augusta University and Emory University School of Medicine, in Atlanta, have also collaborated in the work.
Pulmonary edema is an abnormal accumulation of fluid in the lungs that results in shortness of breath, is life-threatening, and occurs in patients with acute respiratory distress syndrome and COVID-19. This accumulation of fluid causes a lack of oxygenation of the blood and is related to defects in the functioning of the sodium channels responsible for regulating water levels inside and outside the cells.
A collaboration led by Dr. Maria Macias, ICREA researcher and head of the Structural Characterization of Macromolecular Assemblies laboratory at IRB Barcelona, and Dr. Susan Tzotzos, from the Austrian biotech APEPTICO, has revealed the structure of solnatide, a molecule that is being being tested for the treatment of pulmonary edema. Specifically, this project has made it possible to detail the mechanism of interaction of sonatide with the ENaC sodium channel of the cell, responsible for the elimination of pulmonary fluid.
The APEPTICO company from Vienna (Austria), owner of solnatide, has been working with this molecule for many years, studying its biological function. At the moment, the molecule is in the clinical trial phase to treat pulmonary edema in patients with Acute Respiratory Distress Syndrome (ARDS), as well as severe COVID-19 patients with ARDS.
"Our work has focused on describing the structure of the peptide and proposing a mechanism of action to open the door to possible improvements in its sequence, that is, to small modifications that can make it more effective," explains Dr. Macías.
A helix and a dipole
The structure of the sodium channel in cells was already partially described, but there remained a less structured region that was not yet known. In this work, published in the Computational and Structural Biotechnology Journal, the researchers have used structure prediction tools including Alphafold, to identify a helical region aligned with the cell membrane, by the cytoplasmic part. That helix would have a positively charged region and a negatively charged region.
The solnatide, for its part, also had a region called a "dipole", with a negative and a positive charge. Thus, the researchers were able to predict that this would be the point of interaction between both structures and how they were positioned for that interaction.
Researchers from the Catalan biotech BCN Peptides in Barcelona (Spain), and from the American universities Medical College of Georgia at Augusta University and Emory University School of Medicine, in Atlanta, have also collaborated in the work.
Responsible
Juan Bautista Barroso Albarracín
Catedrático UJA
Participants
Roberto García Ruiz
Catedrático UJA
Miguel Delgado Rodríguez
Catedrático UJA
Francisco Luque Vázquez
Catedrático UJA
Sebastián Sánchez Villasclaras
Catedrático UJA
Francisco José Torres Ruiz
Catedrático UJA
Antonio Molina Díaz
Catedrático UJA
Juan Gómez Ortega
Catedrático UJA
José Juan Gaforio Martínez
Catedrático UJA
