An Infrared Reflection-Absorption Spectroscopy Study of the Secondary Structure in (KL4)4K, a Therapeutic Agent for Respiratory Distress Syndrome, in Aqueous Monolayers with Phos
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- 作者：Peng Cai ; Carol R. Flach ; and Richard Mendelsohn
- 刊名：Biochemistry
- 出版年：2003
- 出版时间：August 12, 2003
- 年：2003
- 卷：42
- 期：31
- 页码：9446 - 9452
- 全文大小：151K
- 年卷期：v.42,no.31(August 12, 2003)
- ISSN：1520-4995
文摘
KLLLLKLLLLKLLLLKLLLLK (KL4) has been suggested to mimic some aspects of thepulmonary surfactant protein SP-B and has been tested clinically as a therapeutic agent for respiratorydistress syndrome in premature infants [Cochrane, C. G., and Revak, S. D. (1991) Science 254, 566-568]. It is of obvious interest to understand the mechanism of KL4 function as a guide for design ofimproved therapeutic agents. Attenuated total reflection (ATR) IR measurements have indicated that KL4is predominantly 
-helical with a transmembrane orientation in lipid multilayers (1), a geometry quitedifferent from the originally proposed peripheral membrane lipid interaction. However, the lipid multilayermodel required for ATR may not be the best experimental paradigm to mimic the in vivo function ofKL4. In the current experiments, IR reflection-absorption spectroscopy (IRRAS) was used to evaluatepeptide secondary structure in monolayers at the air/water interface, the physical state that best approximatesthe alveolar lining. In contrast to the ATR-IR results, KL4 (2.5-5 mol %) films with either DPPC orDPPC/DPPG (7/3 mol ratio) adopted an antiparallel 
-sheet structure at all surface pressures studied 
5mN/m, including pressures physiologically relevant for lung function (40-72 mN/m). In contrast, in DPPG/KL4 films, the dominant conformation was the -helix over the entire pressure range, a possible consequenceof enhanced electrostatic interactions. IRRAS has thus provided unique molecular structure informationand insight into KL4/lipid interaction in a physiologically relevant state. A structural model is proposedfor the response of the peptide to surface pressure changes.
-helical with a transmembrane orientation in lipid multilayers (1), a geometry quitedifferent from the originally proposed peripheral membrane lipid interaction. However, the lipid multilayermodel required for ATR may not be the best experimental paradigm to mimic the in vivo function ofKL4. In the current experiments, IR reflection-absorption spectroscopy (IRRAS) was used to evaluatepeptide secondary structure in monolayers at the air/water interface, the physical state that best approximatesthe alveolar lining. In contrast to the ATR-IR results, KL4 (2.5-5 mol %) films with either DPPC orDPPC/DPPG (7/3 mol ratio) adopted an antiparallel -sheet structure at all surface pressures studied 5mN/m, including pressures physiologically relevant for lung function (40-72 mN/m). In contrast, in DPPG/KL4 films, the dominant conformation was the -helix over the entire pressure range, a possible consequenceof enhanced electrostatic interactions. IRRAS has thus provided unique molecular structure informationand insight into KL4/lipid interaction in a physiologically relevant state. A structural model is proposedfor the response of the peptide to surface pressure changes.