High-Throughput Quality Control Assay for the Solid-Phase Synthesis of DNA-Encoded Libraries of Macrocycles*.
Angew Chem Int Ed Engl
; 60(21): 11983-11990, 2021 05 17.
Article
in En
| MEDLINE
| ID: mdl-33682283
ABSTRACT
There is considerable interest in the development of libraries of scaffold-diverse macrocycles as a source of ligands for difficult targets, such as protein-protein interaction surfaces. A classic problem in the synthesis of high-quality macrocyclic libraries is that some linear precursors will cyclize efficiently while some will not, depending on their conformational preferences. We report here a powerful quality control method that can be employed to readily distinguish between scaffolds that do and do not cyclize efficiently during solid-phase synthesis of thioether macrocycles without the need for tedious liquid chromatography/mass spectrometry analysis. We demonstrate that this assay can be employed to identify linear impurities in a DNA-encoded library of macrocycles. We also use the method to establish a useful quality control protocol for re-synthesis of putative macrocyclic screening hits.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA
/
Macrocyclic Compounds
/
Solid-Phase Synthesis Techniques
/
Immobilized Nucleic Acids
Language:
En
Journal:
Angew Chem Int Ed Engl
Year:
2021
Document type:
Article
Affiliation country:
United States