Department of Chemistry, University of Turku, 20014 Turku, Finland.
Org Lett. 2020 Sep 4;22(17):6714-6718. doi: 10.1021/acs.orglett.0c01815. Epub 2020 Aug 17.
The formation of -methoxyoxazolidines in the preparation of oligonucleotide-peptide conjugates was evaluated. The reaction occurred between unprotected 2'--(methoxy)amino-modified oligonucleotides and peptide aldehydes in reasonable yields when isolated. The reaction is reversible under slightly acidic conditions, and it is pH-responsive. The rate and the equilibrium constant may be varied with structurally different aldehydes, allowing an optimization of the ligation and cleavage rate of the resultant conjugates. Therefore, this concept can be considered a cleavable linker.
评估了在寡核苷酸-肽缀合物的制备中 -甲氧基恶唑烷的形成。当分离时，未保护的 2'-（甲氧基）氨基修饰的寡核苷酸与肽醛之间以合理的收率发生反应。在略酸性条件下，反应是可逆的，并且对 pH 有响应。反应速率和平衡常数可能随结构不同的醛而变化，从而可以优化所得缀合物的连接和裂解速率。因此，可以认为该概念是一种可裂解的连接子。
