Solution Phase Synthesis of the Pulmonary Surfactant KL_4: A 21 Amino Acid Synthetic Protein

摘要

The synthetic 21-amino acid polypeptide KL4 [(KL4)4K] was developed as a pulmonary surfactant to be used in treatment of respiratory distress syndrome (RDS) in infants (IRDS) and in adults (ARDS). KL4 is designed to contain intermittent hydrophobic (Leucine) and hydrophilic (Lysine) regions to mimic the structure of the natural surfactant protein B (SP-B). The solution phase synthesis of KL4 is a challenging task. The protection and deprotection patterns, the possibility of diastereomer formation in every coupling step, the solubility (or lack of it) of the different fragments and the isolation of intermediates are among the potential problems that face such a synthesis. The process research work resulted in a successful and efficient large scale synthesis of KL4 which will be discussed.