Basabe-Burgos Oihana, Landreh Michael, Rising Anna, Curstedt Tore
Department of Biosciences and Nutrition, Karolinska Institutet, Neo, 141 83 Huddinge, Sweden.
Science for Life Laboratory, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Tomtebodavägen 23A, SE-171 65 Stockholm, Sweden.
ACS Chem Biol. 2021 Dec 17;16(12):2864-2873. doi: 10.1021/acschembio.1c00816. Epub 2021 Dec 8.
Treatment of respiratory distress syndrome (RDS) with surfactant replacement therapy in prematurely born infants was introduced more than 30 years ago; however, the surfactant preparations currently in clinical use are extracts from animal lungs. A synthetic surfactant that matches the currently used nature-derived surfactant preparations and can be produced in a cost-efficient manner would enable worldwide treatment of neonatal RDS and could also be tested against lung diseases in adults. The major challenge in developing fully functional synthetic surfactant preparations is to recapitulate the properties of the hydrophobic lung surfactant proteins B (SP-B) and SP-C. Here, we have designed single polypeptides that combine properties of SP-B and SP-C and produced them recombinantly using a novel solubility tag based on spider silk production. These Combo peptides mixed with phospholipids are as efficient as nature-derived surfactant preparations against neonatal RDS in premature rabbit fetuses.
30多年前就已开始在早产婴儿中使用表面活性剂替代疗法治疗呼吸窘迫综合征（RDS）；然而，目前临床使用的表面活性剂制剂是从动物肺中提取的。一种能与目前使用的天然来源表面活性剂制剂相匹配且能以经济高效方式生产的合成表面活性剂，将能够在全球范围内治疗新生儿RDS，还可用于针对成人肺部疾病的测试。开发功能完备的合成表面活性剂制剂的主要挑战在于重现疏水性肺表面活性蛋白B（SP-B）和SP-C的特性。在此，我们设计了兼具SP-B和SP-C特性的单一多肽，并利用基于蜘蛛丝生产的新型溶解度标签进行重组生产。这些与磷脂混合的组合肽在早产兔胎儿中治疗新生儿RDS的效果与天然来源表面活性剂制剂一样有效。
