Cycloaddition-promoted self-assembly of a polymer into well-defined beta sheets and hierarchical nanofibrils.
Cycloaddition-promoted self-assembly of a polymer into well-defined beta sheets and hierarchical nanofibrils.
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DOI：
10.1002/anie.200805009
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发表时间：
2009
影响因子：
16.6
通讯作者：
Guan, Zhibin
中科院分区：
文献类型：
--
作者：
Yu, Ting-Bin;Bai, Jane Z.;Guan, Zhibin
尽管生物聚合物，如蛋白质，因其明确的二级、三级和四级结构而无处不在，[1]设计能够折叠成可预测的更高结构的合成聚合物仍然是一个根本的挑战。我们实验室的一个主要研究领域是将弱力引入聚合物中，以引导它们组装成定义良好的分子结构和纳米结构。[2]我们报道了基于Titin的模块化设计的仿生多结构域聚合物。[3]在本研究中，我们的注意力集中在β-Sheet聚合物上。尽管在设计具有β-Sheet结构的离散短肽仿制低聚物方面取得了重大进展，但对材料化学家来说，能够折叠成定义明确的β片状和分级纳米结构的合成高聚合物的设计在很大程度上仍然是虚幻的。β片状结构不仅是蛋白质的基本二级结构，也是许多纤维生物材料的重要结构基序，如淀粉样蛋白[5]和丝素。[6]它们的层次化纳米结构和优异的机械性能启发了仿生材料的设计。[7]尽管许多与肽相关的系统被报道形成了基于β片状结构的纤维，但它们大多是短肽[8]或多肽-聚合物结合物。[9]这些系统中的自组装通常在分子间进行，形成相对较弱的结构。通过重组技术合成的基因工程多肽被报道形成β片状和各种其他纳米结构。然而，这些物种的效率和通用性受到生物合成途径的限制。为了基本利益和先进材料的设计，开发有效的合成方法以获得定义明确的共价键合β-Sheet聚合物是非常必要的。在这里，我们描述了一种新的策略来构建共价合成聚合物，这些聚合物折叠成定义良好的β片断，然后进一步组装成分级纳米纤维(图1)。为此，我们使用了铜(I)催化的叠氮-炔环加成(CuAAC，单击化学)来聚合多肽单体(图1)。CuAAc是一种通用的方法，因为它的效率、官能团耐受性和对各种底物的适用性。[11]自从最初报道这种方法以来，[11a，b]该反应已被广泛应用于广泛的应用，包括选择性连接、[12]生物偶联、[13]分子识别、[14]以及材料和聚合物合成。[15，16]基于结构相似性，叠氮-炔环加成形成的1，4-和1，5-二取代1，2，3-三唑环已被用作α-螺旋线圈中的仿生肽替代物[17]，[18]β链，[19]β-Turn模拟物，[20，21]和假体蛋白。[22]尽管有这些进展，但应该注意的是，这里描述的工作是应用这种化学方法在合成高聚合物中诱导高阶结构形成的第一个例子。我们的设计是基于我们团队最近开发的基于CuAAC反应的收敛β-Turn模拟。结果表明，在非质子介质中，以叠氮和炔基为端基的两个短肽链之间的环加成反应形成1，4-二取代的1，2，3-三氮唑环，从而形成β-Turn结构。[21]1H核磁共振、傅立叶变换红外光谱和分子力学计算表明，1，4-二取代三氮唑的三碳连接基最有利于β-Turn结构的形成。我们推测，如果制备AB肽单体(A=叠氮，B=乙炔)，[2+3]偶极环加成不仅会影响单体的有效聚合，而且还应该
Whereas biopolymers, such as proteins, are ubiquitous for well-defined secondary, tertiary, and quaternary structures,[1] it remains a fundamental challenge to design synthetic polymers that can fold into predictable higher structures. One major area of research in our laboratory is aimed at incorporating weak forces into polymers to guide their assembly into well-defined molecular structures and nanostructures.[2] We reported biomimetic multidomain polymers following modular design of titin.[3] In this study, our attention was drawn to β-sheet polymers. Although significant progress has been made in the area of designing discrete short peptidomimetic oligomers with β-sheet structures,[4] the design of synthetic high polymers that can fold into welldefined β sheets and hierarchical nanostructures remains largely illusive to materials chemists. The β sheet is not only a basic secondary structure in proteins, but also an important structural motif in many fibril biomaterials, such as amyloids [5] and silks.[6] Their hierarchical nanostructures and excellent mechanical properties have inspired biomimetic material designs.[7] Even though a number of peptide-related systems were reported to form β-sheet-based fibrils, most of them are short peptides [8] or peptide–polymer conjugates.[9] The selfassembly in these systems usually proceeds intermolecularly, forming relatively weak structures. Genetically engineered polypeptides, synthesized by recombinant DNA technology, were reported to form β sheets and various other nanostructures.[10] However, the efficiency and versatility of such species are limited by the biosynthetic pathway. Both for fundamental interest and for the design of advanced materials, it is highly desirable to develop efficient syntheses to access well-defined covalently bonded β-sheet polymers. Herein we describe a new strategy to construct covalent synthetic polymers that fold into well-defined β sheets and further assemble into hierarchical nanofibrils (Figure 1).To this end, we employed copper (I)-catalyzed azide–alkyne cycloaddition (CuAAC,“click” chemistry) for polymerization of a peptide monomer (Figure 1). CuAAC is a versatile methodology because of its efficiency, functionalgroup tolerance, and applicability to a wide range of substrates.[11] Since initial reports of this method,[11a, b] the reaction has been employed in a wide range of applications, including selective ligation,[12] bioconjugation,[13] molecular recognition,[14] and material and polymer synthesis.[15, 16] Based on structural similarities, 1, 4-and 1, 5-disubstituted 1, 2, 3-triazole rings formed by azide–alkyne cycloaddition have been used as biomimetic peptide surrogates [17] in α-helical coils,[18] β strands,[19] β-turn mimics,[20, 21] and prosthetic proteins.[22] Despite these developments, it should be noted that the work described here represents the first example of applying this chemistry to induce high-order structure formation in synthetic high polymers. Our design is based on a convergent β-turn mimic that our group recently developed, based on the CuAAC reaction. We have shown that cycloaddition between two short peptide strands terminated with azide and alkyne groups forms a 1, 4-disubstituted 1, 2, 3-triazole ring that induces β-turn formation.[21] 1HNMR and FTIR spectroscopies and molecular mechanics calculations revealed that three-carbon linkers for 1, 4-disubstituted triazole are optimal for the formation of the β-turn structure in nonprotic media. We reasoned that, if an AB peptide monomer was prepared (A= azide, B= acetylene),[2+ 3] dipolar cycloaddition would not only effect efficient polymerization of the monomer, but should also
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影响因子：
15
作者：
Angell, Yu;Chen, Dianjun;Burgess, Kevin
通讯作者：
Burgess, Kevin
影响因子：
16.6
作者：
Jahnke, Eike;Lieberwirth, Ingo;Frauenrath, Holger
通讯作者：
Frauenrath, Holger
影响因子：
2.9
作者：
HARIS, PI;CHAPMAN, D
通讯作者：
CHAPMAN, D
影响因子：
56.9
作者：
Guerette, PA;Ginzinger, DG;Gosline, JM
通讯作者：
Gosline, JM
影响因子：
3.6
作者：
Angell, Y;Burgess, K
通讯作者：
Burgess, K