Onda Yuichi, Bassi Gabriele, Elsayed Abdullah, Ulrich Franziska, Oehler Sebastian, Plais Louise, Scheuermann Jörg, Neri Dario
Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 4, 8093, Zürich, Switzerland.
Philochem AG, Libernstrasse 3, 8112, Otelfingen, Switzerland.
Chemistry. 2021 Apr 26;27(24):7160-7167. doi: 10.1002/chem.202005423. Epub 2021 Mar 18.
The synthesis and characterization of a novel DNA-encoded library of macrocyclic peptide derivatives are described; the macrocycles are based on three sets of proteinogenic and non-proteinogenic amino acid building blocks and featuring the use of copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction for ring closure. The library (termed YO-DEL) which contains 1 254 838 compounds, was encoded with DNA in single-stranded format and was screened against target proteins of interest using affinity capture procedures and photocrosslinking. YO-DEL selections yielded specific binders against serum albumins, carbonic anhydrases and NKp46, a marker of activated Natural Killer cells.
描述了一种新型大环肽衍生物的DNA编码文库的合成与表征；这些大环基于三组蛋白质原性和非蛋白质原性氨基酸构建块，并采用铜（I）催化的炔烃-叠氮化物环加成（CuAAC）反应进行环化。该文库（称为YO-DEL）包含1 254 838种化合物，以单链形式用DNA编码，并使用亲和捕获程序和光交联针对感兴趣的靶蛋白进行筛选。YO-DEL筛选产生了针对血清白蛋白、碳酸酐酶和活化自然杀伤细胞的标志物NKp46的特异性结合剂。
