Department of Chemistry and Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Brendstrupgårdsvej 21A, 8200, Aarhus N, Denmark.
Angew Chem Int Ed Engl. 2023 Jun 5;62(23):e202303170. doi: 10.1002/anie.202303170. Epub 2023 Apr 27.
A method for automated solid-phase synthesis of oligo(disulfide)s was developed. It is based on a synthetic cycle comprising removal of a protecting group from a resin-bound thiol followed by treatment with monomers containing a thiosulfonate as an activated precursor. For ease of purification and characterization, the disulfide oligomers were synthesized as extensions of oligonucleotides on an automated oligonucleotide synthesizer. Six different dithiol monomer building blocks were synthesized. Sequence-defined oligomers of up to seven disulfide units were synthesized and purified. The sequence of the oligomer was confirmed by tandem MS/MS analysis. One of the monomers contains a coumarin cargo that can be released by a thiol-mediated release mechanism. When the monomer was incorporated into an oligo(disulfide) and subjected to reducing conditions, the cargo was released under near-physiological conditions, which underlines the potential use of these molecules in drug delivery systems.
开发了一种用于寡二硫键的自动化固相合成方法。它基于一个合成循环，包括从树脂结合的硫醇上去除保护基团，然后用含有硫代硫酸盐作为激活前体的单体进行处理。为了便于纯化和表征，将二硫键寡聚物作为在自动化寡核苷酸合成仪上的寡核苷酸的延伸来合成。合成了六个不同的二硫醇单体砌块。合成并纯化了多达七个二硫键单元的序列定义的寡聚物。通过串联 MS/MS 分析确认寡聚物的序列。其中一个单体含有香豆素货物，可以通过硫醇介导的释放机制释放。当该单体被掺入到寡二硫键中并处于还原条件下时，货物在近生理条件下释放，这突出了这些分子在药物传递系统中的潜在用途。
