Walther Frans J, Gordon Larry M, Waring Alan J
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Biomed Hub. 2016 Sep-Dec;1(3):1-21. doi: 10.1159/000451076. Epub 2016 Nov 16.
Surfactant protein (SP)-B is a 79-residue polypeptide crucial for the biophysical and physiological function of endogenous lung surfactant. SP-B is a member of the Saposin or Saposin-like proteins (SAPLIP) family of proteins that share an overall three-dimensional folding pattern based on secondary structures and disulfide connectivity and exhibit a wide diversity of biological functions. Here we review the synthesis, molecular biophysics and activity of synthetic analogs of Saposin proteins designed to mimic those interactions of the parent proteins with lipids that enhance interfacial activity. Saposin proteins generally interact with target lipids as either monomers or multimers via well-defined amphipathic helices, flexible hinge domains, and insertion sequences. Based on the known 3D-structural motif for the Saposin family, we show how bioengineering techniques may be used to develop minimal peptide constructs that maintain desirable structural properties and activities in biomedical applications. One important application is the molecular design, synthesis and activity of Saposin mimics based on the SP-B structure. Synthetic lung surfactants containing active SP-B analogs may be potentially useful in treating diseases of surfactant deficiency or dysfunction including the neonatal respiratory distress syndrome and acute lung injury/acute respiratory distress syndrome.
表面活性蛋白（SP）-B是一种由79个氨基酸残基组成的多肽，对内源性肺表面活性剂的生物物理和生理功能至关重要。SP-B是鞘脂激活蛋白或鞘脂激活蛋白样蛋白（SAPLIP）家族的成员，该家族蛋白质基于二级结构和二硫键连接共享整体三维折叠模式，并表现出广泛多样的生物学功能。在此，我们综述了旨在模拟亲本蛋白与脂质相互作用以增强界面活性的鞘脂激活蛋白合成类似物的合成、分子生物物理学及活性。鞘脂激活蛋白通常通过明确的两亲性螺旋、柔性铰链结构域和插入序列以单体或多聚体形式与靶脂质相互作用。基于鞘脂激活蛋白家族已知的三维结构基序，我们展示了如何利用生物工程技术开发在生物医学应用中保持所需结构特性和活性的最小肽构建体。一个重要应用是基于SP-B结构的鞘脂激活蛋白模拟物的分子设计、合成及活性。含有活性SP-B类似物的合成肺表面活性剂可能对治疗包括新生儿呼吸窘迫综合征和急性肺损伤/急性呼吸窘迫综合征在内的表面活性剂缺乏或功能障碍性疾病具有潜在用途。
