Work

Streamlined construction of peptide macrocycles via palladium-catalyzed intramolecular S -arylation in solution and on DNA

Year: 2021

Type: article

Abstract: -arylation of alkyl and aryl thiols with aryl iodides under mild conditions is developed. The method exhibits a broad substrate scope for thiols, aryl iodides and amino acid units. Peptide macrocycles of a wide range of size and composition can be readily assembled in high yield from various easily accessible building blocks. This method has been successfully employed to prepare an 8-million-membered tetrameric cyclic peptide DNA-encoded library (DEL). Preliminary screening of the DEL library against protein p300 identified compounds with single digit micromolar inhibition activity.

Source: Chemical Science

DOI: 10.1039/d1sc00789k

Authors: Peng Yang, Xuan Wang, Bo Li, Yixuan Yang, Jinfeng Yue, Yanrui Suo, Huarong Tong, Gang He, Xiaojie Lu, Gong Chen

Institutions: Nankai University, Chinese Academy of Sciences, Shanghai Institute of Materia Medica, State Key Laboratory of Drug Research

Language: English

Topic: Chemical Synthesis and Analysis

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: diamond

Funders: National Natural Science Foundation of China, Ministry of Education of the People's Republic of China, Nankai University, Natural Science Foundation of Tianjin City, National Key New Drug Creation and Manufacturing Program, Ministry of Science and Technology

Awards: G2286454255, G2889761189, G3470832224, G410247322, G4310161818, 复杂环肽分子的合成研究, G4363245776, G492479846, G5188723346, G5362630973, G6387123747, G711335526, G7158117070, G7622131228, G7650739732, G8960142504

OpenAlex ID: W3136049665

FWCI: 3.556

Cites: 103

Cited by: 61

Related to: 10