Mismatched covalent and noncovalent templating leads to large coiled coil-templated macrocycles.
Mismatched covalent and noncovalent templating leads to large coiled coil-templated macrocycles.
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DOI：
10.1039/d3sc00231d
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发表时间：
2023-05-10
期刊：
影响因子：
8.4
通讯作者：
中科院分区：
文献类型：
--
作者：
在这里，我们描述了使用动态组合化学来自组装复杂的螺旋线圈基元。我们将一系列设计成与3，5-二硫代苯甲酸(B)在N-末端形成同源二聚体卷曲的多肽进行酰胺偶联，然后允许每个B-肽进行二硫键交换。在没有肽的情况下，单体B形成环状三聚体和四聚体，因此我们预计，将肽添加到单体B中将使平衡向四聚体移动，以最大限度地形成卷曲。出人意料的是，我们发现，通过盘绕形成的B-肽的内部模板将平衡向更大的大环移动，最多13个B-肽亚基，倾向于4、7和10个成员的大环。与分子间盘绕的同源二聚体相比，这些大环组件显示出更大的螺旋度和热稳定性。对大大环的偏好是由盘绕线圈的强度驱动的，因为增加盘绕线圈的亲和力增加了大大环的比例。该系统代表了一种开发复杂多肽和蛋白质组件的新方法。在动态组合文库中结合两种不同的驱动力--α-螺旋螺旋二聚体形成和共价三聚体和四聚体形成--导致了高达13个亚基的大环的意外组装。
Herein we describe the use of dynamic combinatorial chemistry to self-assemble complex coiled coil motifs. We amide-coupled a series of peptides designed to form homodimeric coiled coils with 3,5-dithiobenzoic acid (B) at the N-terminus and then allowed each B-peptide to undergo disulfide exchange. In the absence of peptide, monomer B forms cyclic trimers and tetramers, and thus we expected that addition of the peptide to monomer B would shift the equilibrium towards the tetramer to maximize coiled coil formation. Unexpectedly, we found that internal templation of the B-peptide through coiled coil formation shifts the equilibrium towards larger macrocycles up to 13 B-peptide subunits, with a preference for 4, 7, and 10-membered macrocycles. These macrocyclic assemblies display greater helicity and thermal stability relative to intermolecular coiled coil homodimer controls. The preference for large macrocycles is driven by the strength of the coiled coil, as increasing the coiled coil affinity increases the fraction of larger macrocycles. This system represents a new approach towards the development of complex peptide and protein assemblies. Combining two different driving forces in a dynamic combinatorial library – alpha-helical coiled coil dimer formation and covalent trimer and tetramer formation – leads to unexpected assembly of macrocycles up to 13 subunits.
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影响因子：
7.8
作者：
Henchey, Laura K.;Jochim, Andrea L.;Arora, Paramjit S.
通讯作者：
Arora, Paramjit S.
影响因子：
56.9
作者：
Carnall, Jacqui M. A.;Waudby, Christopher A.;Otto, Sijbren
通讯作者：
Otto, Sijbren
DOI：
10.1073/pnas.1710695114
发表时间：
2017-10-10
影响因子：
11.1
作者：
Dang, Bobo;Wu, Haifan;DeGrado, William F.
通讯作者：
DeGrado, William F.
影响因子：
15
作者：
DAWSON, PE;KENT, SBH
通讯作者：
KENT, SBH
影响因子：
2.4
作者：
Giri, Rajat Subhra;Pal, Saikat;Mandal, Bhubaneswar
通讯作者：
Mandal, Bhubaneswar