Department of Chemistry, The University of Texas at Austin, Austin, TX 78712, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Chemistry. 2023 Oct 13;29(57):e202301949. doi: 10.1002/chem.202301949. Epub 2023 Sep 8.
The creation of complementary products via templating is a hallmark feature of nucleic acid replication. Outside of nucleic acid-like molecules, the templated synthesis of a hetero-complementary copy is still rare. Herein we describe one cycle of templated synthesis that creates homomeric macrocyclic peptides guided by linear instructing strands. This strategy utilizes hydrazone formation to pre-organize peptide oligomeric monomers along the template on a solid support resin, and microwave-assisted peptide synthesis to couple monomers and cyclize the strands. With a flexible templating strand, we can alter the size of the complementary macrocycle products by increasing the length and number of the binding peptide oligomers, showing the potential to precisely tune the size of macrocyclic products. For the smaller macrocyclic peptides, the products can be released via hydrolysis and characterized by ESI-MS.
通过模板合成互补产品是核酸复制的一个显著特征。在类似核酸的分子之外，异源互补拷贝的模板合成仍然很少见。在此，我们描述了一个模板合成循环，该循环在指导线性链的引导下，通过同源寡聚环肽的形成来合成同型大环肽。该策略利用腙键形成将肽寡聚单体预组织在固体支撑树脂上的模板上，然后通过微波辅助肽合成将单体偶联并环化。通过灵活的模板链，我们可以通过增加结合肽寡聚物的长度和数量来改变互补大环产物的大小，显示出精确调节大环产物大小的潜力。对于较小的环状多肽，可以通过水解释放产物，并通过 ESI-MS 进行表征。
