Concerning the article by T. Curstedt and J. Johansson: new synthetic surfactants - basic science.

Abstract

from the N-terminus of SP-C, with added stretches of leucines and lysines to create an -helix-like conformation, improved in vitro and in vivo function in premature rabbit fetuses when mixed with phospholipids. Another SP-B peptide, SP-B 1–25 and dimeric SP-B 1–25, has also been reported to improve static lung compliance in premature rabbits [11] , although no clinical studies using this modifi ed SP-B peptide have been reported. Because of the enhanced resistance to inhibition observed with KL 4 peptide surfactant (lucinactant) [12–14] , we agree with the authors that this synthetic peptide surfactant should be effective in the treatment of meconium aspiration syndrome. The SP-B-like peptide surfactant was active in 39 preterm infants treated for respiratory distress syndrome [15] . And most recently this surfactant has demonstrated positive results in two randomized trials in more than 1,400 preterm infants comparing lucinactant with a previously used synthetic surfactant, Exosurf, and two animal-derived surfactants, Survanta and Curosurf, for the prevention of respiratory distress syndrome [16, 17] . We hypothesize that this robust effi cacy response is due to observations suggesting that the novel, SP-B-derived, KL 4 peptide in lucinactant confers both strong function and a unique resistance to inhibition [11, 13, 14] . Dear Sir, In their review of the newer synthetic surfactants, Curstedt and Johansson [1] imply that the lysine-leucine peptide (KL 4 ) by Cochrane and Revak [2] extensively characterized in vitro and tested in a number of randomized clinical trials resembles SP-C rather than SP-B based on the report of Gustafsson et al. [3] . This study used Fourier-transformed infrared spectral analysis in phospholipid bilayers rather than in the monolayer in which SP-B functions in alveolar expansion as noted previously [4] . In phospholipid monolayers, KL 4 conforms to the natural SP-B sequence, in particular, residues 64–79 with the intermittent basic residues and the multiplicity of leucines in the hydrophobic stretches being near duplicates of the C-terminus of SP-B. These multiple lysines (or arginines) along with hydrophobic amino acid stretches permit KL 4 peptide to function within the surfactant phospholipid monolayer as an effective synthetic SP-B mimic. SP-B is essential for surfactant function and viability at birth in human beings [5, 6] and in mice [7] , while mice [8] or humans [9] with an absence of SP-C expression have normal ventilatory function at birth, but later develop interstitial disease. Studies by Cochrane and co-workers [2, 10] indicate that function of the SP-B-like peptides requires the presence of intermittent basic amino acid residues, arginine or lysine. It is, therefore, not surprising that a peptide derived Published online: December 6, 2005