Nephrilin peptides have proven to have several beneficial systemic effects in rodent models of stress, burn, and sepsis by reducing present pro-inflammatory factors. Scientists in Sunnyvale, CA were keen on testing these nephrilin-class peptides on models of respiratory distress, applying their beneficial properties to rat scald-endotoxemia models. LifeTein synthesized specially designed peptides with Valproic acid covalently attached to the N-terminus to be tested on the scald-endotoxemia models.

Valporic Acid Enhances Nephrilin Peptides

Three peptides in total were synthesized for the group by LifeTein, Nmod3sN1v, Nmod3N1vA, and Nmod3N1vAS3, whose sequences can be seen in the figure. The latter two peptides differ from Nmod3sN1v in that they contain the tripeptide sequence d(AVD), since the tripeptide has shown to dramatically improve iron-binding in vitro. Nmod3N1vAS3 differs from Nmod3N1vA in that it contains a Y*LK motif (where Y* is phosphotyrosine). This motif was previously shown to inhibit STAT3 activation, a suspected role in lung inflammation pathology.

After treating the rat scald-endotoxemia models with the peptides, the group concluded that the Nmod3N1vA and Nmod3N1vAS3 peptides were superior than the Nmod3sN1v sequence in the following readings: protease-stability, biodistribution to lung tissue, amelioration of catabolism, early inflammation and insulin-resistance, activated lymph node dendritic / T-cells, breathing difficulty (by oximetry), lung edema, granulocyte count and IL1-beta in BAL fluid, systemic oxidative stress and kidney function. The group concluded that when compared to the original nephrilin peptide, these designs are at least ten times more potent by weight. The study showcases the potential these peptide designs hold for future drug development, especially in respiratory models and burn damage.

References: Desmond D. Mascarenhas, Puja Ravikumar, Edward P. Amento, N-modulin peptides attenuate respiratory distress in a scald-endotoxemia model, Burns Open, Volume 6, Issue 1, 2022, Pages 1-6, ISSN 2468-9122, https://doi.org/10.1016/j.burnso.2021.09.001.