Helix macrodipole control of β3-peptide 14-helix stability in water
Helix macrodipole control of β3-peptide 14-helix stability in water
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DOI：
10.1021/ja029868a
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发表时间：
2003-04-09
影响因子：
15
通讯作者：
Schepartz, A
中科院分区：
文献类型：
--
作者：
Hart, SA;Bahadoor, ABF;Schepartz, A
β-肽由于能够在甲醇中填充螺旋二级结构，即使在没有稳定的三级相互作用的情况下也引起了相当大的关注。最近在β-肽设计方面所做的努力很少产生在水中形成稳定的14-螺旋的β3-肽；那些确实需要在三个螺旋面中的两个上稳定分子内盐桥的那些，因此在生物学研究中作为工具的实用性有限。在这里，我们表明，与14-螺旋大偶极子的有利相互作用显著稳定了水中的14-螺旋，减少了在三个螺旋面中的两个面上需要多个盐桥。我们还报道了以前未知的γ-分支β3-氨基酸对14-螺旋结构的稳定作用。我们描述的最具结构的分子在初级序列水平上是高度异质的，在一个11个残基的序列中包含7个不同的β3-氨基酸。这些结果代表了设计折叠良好的14-螺旋的关键的第一步，该设计探索了β3-肽与生物大分子在体外和体内的相互作用。
β-Peptides have attracted considerable attention by virtue of their ability to populate helical secondary structures in methanol, even in the absence of stabilizing tertiary interactions. Recent efforts in β-peptide design have produced few β3-peptides that form stable 14-helices in water; those that do require stabilizing intramolecular salt bridges on two of three helical faces and therefore possess limited utility as tools in biological research. Here we show that favorable interactions with the 14-helix macrodipole significantly stabilize the 14-helix in water, alleviating the need for multiple salt bridges on two of three helical faces. We also report the previously unrecognized stabilization of 14-helix structure by γ-branched β3-amino acids. The most structured molecules we describe are highly heterogeneous at the primary sequence level, containing seven different β3-amino acids within an 11-residue sequence. These results represent the essential first step toward the design of well-folded 14-helices that explore the interactions between β3-peptides and biological macromolecules in vitro and in vivo.