Deluge Biotechnologies, 6671 W. Indiantown Rd., Suite 50-325, Jupiter, FL 33458, USA.
Department of Chemistry, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USA.
Angew Chem Int Ed Engl. 2022 Apr 25;61(18):e202116999. doi: 10.1002/anie.202116999. Epub 2022 Mar 2.
There is considerable interest in the development of libraries of non-peptidic macrocycles as a source of ligands for difficult targets. We report here the solid-phase synthesis of a DNA-encoded library of several hundred thousand thioether-linked macrocycles. The library was designed to be highly diverse with respect to backbone scaffold diversity and to minimize the number of amide N-H bonds, which compromise cell permeability. The utility of the library as a source of protein ligands is demonstrated through the isolation of compounds that bind Streptavidin, a model target, with high affinity.
人们对开发非肽大环库作为难靶标配体的来源非常感兴趣。我们在此报告了一种固相合成含有数十万个硫醚键大环的 DNA 编码文库。该文库在骨架多样性和最小化酰胺 N-H 键数量方面具有高度多样性，酰胺 N-H 键会影响细胞通透性。该文库作为蛋白质配体的用途通过分离与模型靶标链霉亲和素高亲和力结合的化合物得到证明。
