title: Location of structural transitions in an isotopically labeled lung surfactant SP-B peptide by IRRAS.
abstract: Pulmonary surfactant, a lipid/protein complex that lines the air/water interface in the mammalian lung, functions to reduce the work of breathing. Surfactant protein B (SP-B) is a small, hydrophobic protein that is an essential component of this mixture. Structure-function relationships of SP-B are currently under investigation as the protein and its peptide analogs are being incorporated into surfactant replacement therapies. Knowledge of the structure of SP-B and its related peptides in bulk and monolayer phases will facilitate the design of later generation therapeutic agents. Prior infrared reflection-absorption spectroscopic studies reported notable, reversible surface pressure-induced antiparallel beta-sheet formation in a synthetic peptide derived from human SP-B, residues 9-36 (SP-B(9-36)). In the current work, infrared reflection-absorption spectroscopy is applied in conjunction with isotopic labeling to detect the site and pressure dependence of the conformational change. SP-B(9-36), synthesized with (13)C=O-labeled Ala residues in positions 26, 28, 30, and 32, shifted the beta-sheet marker band to approximately 1600 cm(-1) and thus immediately identified this structural element within the labeled region. Surface pressure-induced alterations in the relative intensities of Amide I band constituents are interpreted using a semiempirical transition dipole coupling model. In addition, electron micrographs reveal the formation of tubular myelin structures from in vitro preparations using SP-B(9-36) in place of porcine SP-B indicating that the peptide has the potential to mimic this property of the native protein.
authors.affiliation: Department of Chemistry, Newark College of Arts and Sciences, Rutgers University, Newark, New Jersey, USA. flach@andromeda.rutgers.edu
authors.forename: Carol R
authors.initials: CR
authors.lastname: Flach
authors.forename: Peng
authors.initials: P
authors.lastname: Cai
authors.forename: Darline
authors.initials: D
authors.lastname: Dieudonné
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Brauner
authors.forename: Kevin M W
authors.initials: KM
authors.lastname: Keough
authors.forename: June
authors.initials: J
authors.lastname: Stewart
authors.forename: Richard
authors.initials: R
authors.lastname: Mendelsohn
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001688:Biological Products / Q000737:chemistry*; D003198:Computer Simulation; D003461:Crystallography / Q000379:methods*; D006801:Humans; D007553:Isotope Labeling; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009186:Myelin Sheath; D044367:Phase Transition; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry*; D011663:Pulmonary Surfactants / Q000737:chemistry*; D051381:Rats; D013045:Species Specificity; D013055:Spectrophotometry, Infrared / Q000379:methods*; D013329:Structure-Activity Relationship; D013500:Surface Tension; D013556:Swine, Miniature
chemical_list: D001688:Biological Products; D011506:Proteins; D037701:Pulmonary Surfactant-Associated Protein B; D011663:Pulmonary Surfactants; C018167:tubular myelin