Howard Hughes Medical Institute, Department of Molecular Biology, and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, United States.
J Am Chem Soc. 2022 Oct 12;144(40):18350-18358. doi: 10.1021/jacs.2c06268. Epub 2022 Sep 29.
In all known genetic polymers, molecular recognition via hydrogen bonding between complementary subunits underpins their ability to encode and transmit information, to form sequence-defined duplexes, and to fold into catalytically active forms. Reversible covalent interactions between complementary subunits provide a different way to encode information, and potentially function, in sequence-defined oligomers. Here, we examine six oligoarylacetylene trimers composed of aniline and benzaldehyde subunits. Four of these trimers self-pair to form two-rung duplex structures, and two form macrocyclic 1,3-folded structures. The equilibrium proportions of these structures can be driven to favor each of the observed structures almost entirely depending upon the concentration of trimers and an acid catalyst. Quenching the acidic trimer solutions with an organic base kinetically traps all species such that they can be isolated and characterized. Mixtures of complementary trimers form exclusively sequence-specific 3-rung duplexes. Our results suggest that reversible covalent bonds could in principle guide the formation of more complex folded conformations of longer oligomers.
在所有已知的遗传聚合物中，通过互补亚基之间的氢键进行分子识别是它们能够编码和传递信息、形成序列定义的双链体以及折叠成具有催化活性形式的基础。互补亚基之间的可逆共价相互作用为序列定义的低聚物中的信息编码和潜在功能提供了另一种方式。在这里，我们研究了由苯胺和苯甲醛亚基组成的六个寡芳基乙炔三聚体。其中四个三聚体自组装形成两个梯级双链体结构，两个形成大环 1,3 折叠结构。这些结构的平衡比例可以根据三聚体和酸催化剂的浓度驱动，几乎完全有利于观察到的每种结构。用有机碱猝灭酸性三聚体溶液可以动力学地捕获所有物种，从而可以将它们分离和表征。互补三聚体的混合物形成专一地序列特异性 3 梯级双链体。我们的结果表明，可逆共价键原则上可以指导更长低聚物更复杂折叠构象的形成。
