title: Improvement of pulmonary surfactant activity by introducing D-amino acids into highly hydrophobic amphiphilic α-peptide Hel 13-5.
abstract: The high costs of artificial pulmonary surfactants, ranging in hundreds per kilogram of body weight, used for treating the respiratory distress syndrome (RDS) premature babies have limited their applications. We have extensively studied soy lecithins and higher alcohols as lipid alternatives to expensive phospholipids such as DPPC and PG. As a substitute for the proteins, we have synthesized the peptide Hel 13-5D3 by introducing D-amino acids into a highly lipid-soluble, basic amphiphilic peptide, Hel 13-5, composed of 18 amino acid residues. Analysis of the surfactant activities of lipid-amphiphilic artificial peptide mixtures using lung-irrigated rat models revealed that a mixture (Murosurf SLPD3) of dehydrogenated soy lecithin, fractionated soy lecithin, palmitic acid (PA), and peptide Hel 13-5D3 (40:40:17.5:2.5, by weight) superior pulmonary surfactant activity than a commercially available pulmonary surfactant (beractant, Surfacten®). Experiments using ovalbumin-sensitized model animals revealed that the lipid-amphiphilic artificial peptide mixtures provided significant control over an increase in the pulmonary resistance induced by premature allergy reaction and reduced the number of acidocytes and neutrophils in lung-irrigated solution. The newly developed low-cost pulmonary surfactant system may be used for treatment of a wide variety of respiratory diseases.
authors.affiliation: Muromachi Chemical Co. Ltd., Ohmuta, Fukuoka 836-0895, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Fukuoka University Hospital, Fukuoka 814-0180, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Yukitake
authors.affiliation: Department of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki 859-3298, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Nakahara
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University and Emergency & Critical Care Center, Kyushu University Hospital, Fukuoka 812-8582, Japan.
authors.forename: Sooyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki 859-3298, Japan. Electronic address: wosamu@niu.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Shibata
authors.affiliation: Department of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki 859-3298, Japan; Department of Chemistry, Faculty of Science, Fukuoka University, Fukuoka 814-0180, Japan.
authors.forename: Sannamu
authors.initials: S
authors.lastname: Lee
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D002942:Circular Dichroism; D006461:Hemolysis / Q000187:drug effects*; D057927:Hydrophobic and Hydrophilic Interactions; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D017208:Rats, Wistar
chemical_list: D000596:Amino Acids; C440034:Hel 13-5 peptide; D010455:Peptides; D011663:Pulmonary Surfactants
keywords: Amphiphilic α-helical peptide; Artificial pulmonary surfactant; Recovery of lung compliance; Respiratory distress syndrome; Soy lecithin; Surface tension–area diagram