Srinivas Chamakuri; Mee-Kyung Chung; Errol L. G. Samuel; Kevin A. Tran; Ying-Chu Chen; Pranavanand Nyshadham; Conrad Santini; Martin M. Matzuk; Damian W. Young
Bioorg. Med. Chem., 2021, 116387
https://doi.org/10.1016/j.bmc.2021.116387

Abstract

Here we report the successful construction of a novel, stereochemically diverse DNA-Encoded Chemical Library (DECL) by utilizing 24 enantiomerically pure trifunctional 2, 6- di-substituted piperazines as central cores. We introduce the concept of positional diversity by placing the DNA attachment at either of two possible sites on the piperazine scaffold. Using a wide range of building blocks, a diverse library of 77 million compounds was produced. Cheminformatic analysis demonstrates that this library occupies a wide swath of chemical space, and that the piperazines scaffold confers different shape diversity compared to the commonly used triazine core.