Covalent modification of nephrilin peptide with valproic acid increases its efficacy as a therapeutic in burn trauma

Introduction: Nephrilin peptide, a designed inhibitor of Rictor complex, modulates systemic responses to trauma, alleviating clinically relevant variables in a rat scald model and sepsis mortality in a mouse model. This study explores the possibility that chemical conjugation of small molecules to the aminoterminus of nephrilin can modify its biological activity in the rat scald model. Methods: One of four molecules (valproic acid, decanoic acid, fenofibric acid and ibuprofen) was chemically attached to the amino terminus of nephrilin during synthesis. Animals were treated with each modified nephrilin by subcutaneous bolus injection on days 1–7 post-burn. Results: Compared to nephrilin, valproic acid-modified nephrilin showed significantly (all p