methoxysuccinyl-alanyl-alanyl-prolyl-valine-chloromethyl-ketone and Respiratory-Distress-Syndrome

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the most common complications in COVID-19. Elastase has been recognized as an important target to prevent ALI/ARDS in the patient of COVID-19. Cyclotheonellazole A (CTL-A) is a natural macrocyclic peptide reported to be a potent elastase inhibitor. Herein, we completed the first total synthesis of CTL-A in 24 linear steps. The key reactions include three-component MAC reactions and two late-stage oxidations. We also provided seven CTL-A analogues and elucidated preliminary structure-activity relationships. The

Topics: Acute Lung Injury; Animals; Bleomycin; Cell Line; COVID-19; COVID-19 Drug Treatment; Disease Models, Animal; Humans; Leukocyte Elastase; Male; Mice; Mice, Inbred C57BL; Peptides, Cyclic; Respiratory Distress Syndrome; Serine Proteinase Inhibitors