Biomimetic nanostructures: creating a high-affinity zinc-binding site in a folded nonbiological polymer.

Biomimetic nanostructures: creating a high-affinity zinc-binding site in a folded nonbiological polymer.
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DOI:
10.1021/ja802125x
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发表时间:
2008-07-09
影响因子:
15
通讯作者:
Zuckermann RN
Zuckermann RN
中科院分区:
化学1区
文献类型:
--
作者:
Lee BC;Chu TK;Dill KA;Zuckermann RN

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开发先进生物材料的长期目标之一是从完全非天然的聚合物中产生类似蛋白质的纳米结构和功能。为此,我们在类肽(n -取代甘氨酸聚合物)双螺旋束中引入了高亲和力的锌结合功能。利用蛋白质中众所周知的锌结合基序,巯基和咪唑基序被定位在类肽中,使得两个螺旋必须紧密排列才能形成一个结合位点。我们利用荧光共振能量转移(FRET)报告基团来测量两个螺旋段之间距离的变化,并探测锌的结合。我们系统地改变了锌结合残基的位置和数量,以及连接两个螺旋片段的环的序列和大小。我们发现,与其他二价金属离子相比,某些肽类双螺旋束结合锌具有纳摩尔亲和力和高选择性。我们的工作是朝着产生具有酶样功能的仿生纳米结构迈出的重要一步。
One of the long-term goals in developing advanced biomaterials is to generate protein-like nanostructures and functions from a completely nonnatural polymer. Toward that end, we introduced a high-affinity zinc-binding function into a peptoid (N-substituted glycine polymer) two-helix bundle. Borrowing from well-understood zinc-binding motifs in proteins, thiol and imidazole moieties were positioned within the peptoid such that both helices must align in close proximity to form a binding site. We used fluorescence resonance energy transfer (FRET) reporter groups to measure the change of the distance between the two helical segments and to probe the binding of zinc. We systematically varied the position and number of zinc-binding residues, as well as the sequence and size of the loop that connects the two helical segments. We found that certain peptoid two-helix bundles bind zinc with nanomolar affinities and high selectivity compared to other divalent metal ions. Our work is a significant step toward generating biomimetic nanostructures with enzyme-like functions.
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