Design of Surfactant Protein B Peptide Mimics Based on the Saposin Fold for Synthetic Lung Surfactants.
Design of Surfactant Protein B Peptide Mimics Based on the Saposin Fold for Synthetic Lung Surfactants.
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DOI：
10.1159/000451076
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发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Waring AJ
中科院分区：
文献类型：
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作者：
Walther FJ;Gordon LM;Waring AJ
表面活性蛋白 (SP)-B 是一种 79 个残基的多肽，对于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 是皂苷或皂苷样蛋白 (SAPLIP) 蛋白家族的成员，其共享基于二级结构和二硫键连接的整体三维折叠模式，并表现出广泛多样性的生物学功能。在这里，我们回顾了saposin蛋白的合成类似物的合成、分子生物物理学和活性，这些蛋白的合成类似物旨在模拟母体蛋白与脂质的相互作用，从而增强界面活性。 Saposin 蛋白通常通过明确的两亲性螺旋、灵活的铰链结构域和插入序列以单体或多聚体的形式与靶脂质相互作用。基于saposin家族已知的3D结构基序，我们展示了如何使用生物工程技术来开发最小的肽构建体，以在生物医学应用中保持所需的结构特性和活性。一项重要的应用是基于 SP-B 结构的 Saposin 模拟物的分子设计、合成和活性。含有活性 SP-B 类似物的合成肺表面活性剂可能可用于治疗表面活性剂缺乏或功能障碍的疾病，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。
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.