Synthetic peptide‐containing surfactants

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Abstract
Pulmonary surfactant contains two hydrophobic proteins, SP‐B and SP‐C. With the aim of identifying synthetic SP‐B and SP‐C substitutes for replacement therapy of respiratory distress syndromes, we have studied two transmembrane peptides and two amphipathic peptides that are located in the plane of a phospholipid bilayer. One amphipathic peptide was designed by changing the amino acid sequence, but not the composition or size, of the 21‐residue peptide KL4. This peptide, designated KL2.3 from its spacing of nonpolar and polar residues, exhibited similar α‐helical content as KL4 but was oriented along a phospholipid bilayer plane, in contrast to the transmembrane orientation of KL4 in the same environment. The second amphipathic peptide analyzed was succinyl‐LLEKLLEWLK‐amide (WMAP10). KL4 more efficiently accelerated the spreading of a mixture of 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine (Pam2GroPCho)/phosphatidylglycerol (PtdGro)/palmitic acid (PamOH), 68 : 22 : 9 (by mass), at an air/water interface than did any of the amphipathic peptides. Similarly, KL4, but not KL2.3, when present in an interfacial monolayer composed of Pam2GroPCho/1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphoglycerol, 7 : 3 (by mass), increased lipid insertion from subphase vesicles. An SP‐C analogue, SP‐C(Leu), with all helical valyl residues in native SP‐C replaced with Leu and the palmitoylcysteines at positions 5 and 6 replaced with Ser, but otherwise with essentially the same primary structure as the native peptide, was analyzed. SP‐C(Leu) exhibited similar α‐helical content as native SP‐C and a transmembrane orientation and, in contrast to poly‐valyl‐containing synthetic peptides, it folds into a helical conformation after acid‐induced denaturation. SP‐C(Leu) accelerated the spreading of Pam2GroPCho/PtdGro/PamOH, 68 : 22 : 9 (by mass), almost identically to native SP‐C, and lowered the surface tension during rapid cyclic film compressions in a pulsating bubble surfactometer to near zero and 43 mN/m at minimum and maximum bubble size, respectively. Airway instillation of 2 % (by mass) SP‐C(Leu) combined with Pam2GroPCho/PtdGro/PamOH in preterm rabbit fetuses improved dynamic lung compliance by about 30 % compared with untreated controls.

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