靶向跨膜螺旋的β-肽的计算设计。
Computational design of a β-peptide that targets transmembrane helices.
机构信息
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
出版信息
J Am Chem Soc. 2011 Aug 17;133(32):12378-81. doi: 10.1021/ja204215f. Epub 2011 Jul 22.
Abstract
The design of β-peptide foldamers targeting the transmembrane (TM) domains of complex natural membrane proteins has been a formidable challenge. A series of β-peptides was designed to stably insert in TM orientations in phospholipid bilayers. Their secondary structures and orientation in the phospholipid bilayer was characterized using biophysical methods. Computational methods were then devised to design a β-peptide that targeted a TM helix of the integrin α(IIb)β(3). The designed peptide (β-CHAMP) interacts with the isolated target TM domain of the protein and activates the intact integrin in vitro.
摘要
设计针对复杂天然膜蛋白跨膜（TM）结构域的β-肽折叠物一直是一个艰巨的挑战。设计了一系列β-肽，以稳定地插入磷脂双层中的 TM 取向。使用生物物理方法对它们在磷脂双层中的二级结构和取向进行了表征。然后设计了计算方法来设计针对整合素α(IIb)β(3)的 TM 螺旋的β-肽。设计的肽（β-CHAMP）与蛋白质的分离的靶 TM 结构域相互作用，并在体外激活完整的整合素。
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