Department of Biochemistry and Biophysics, and the Department of Chemistry, University of Pennsylvania, Stellar-Chance Building Room 1010, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104-6059, USA.
J Am Chem Soc. 2009 Mar 11;131(9):3377-84. doi: 10.1021/ja809580b.
The de novo design of molecular switching peptides is of increasing interest because it tests and extends our fundamental understanding of this process while laying the groundwork for the creation of new chemical and biological sensors. Here, an alpha-helical amphiphilic cell-lytic peptide, mastoparan X, was engineered to bind divalent cations. Binding of Zn(II) or Ni(II) to the designed peptide Mst-HH stabilizes the lytic amphiphilic structure and increases the activity of the peptide. Although both Zn(II) and Ni(II) activate Mst-HH for membrane lysis, they appear to do so via different mechanisms. Additionally, a series of metal binding-site mutants were synthesized to assess the relationship of charge and helical propensity to the toxicity and switchability. Additionally, by changing the characteristics of the metal-binding ligands, we can vary the selectivity of the site.
从头设计分子开关肽越来越受到关注，因为它检验和扩展了我们对此过程的基本理解，同时为创建新的化学和生物传感器奠定了基础。在这里，一种α-螺旋两亲性溶细胞肽，mastoparan X，被设计用来结合二价阳离子。Zn(II)或 Ni(II)与设计的肽 Mst-HH 的结合稳定了溶细胞两亲性结构并增加了肽的活性。尽管 Zn(II)和 Ni(II)都能激活 Mst-HH 以促进膜裂解，但它们似乎通过不同的机制来实现。此外，还合成了一系列金属结合位点突变体，以评估电荷和螺旋倾向与毒性和开关能力的关系。此外，通过改变金属结合配体的特性，我们可以改变该位点的选择性。
