Issue 6, 2022

Conjugation of oligonucleotides with activated carbamate reagents prepared by the Ugi reaction for oligonucleotide library synthesis

Abstract

The DNA-encoded library (DEL) is a powerful tool for drug discovery. As a result, to obtain diverse DELs, many DNA-compatible chemical reactions have been developed over the past decade. Among the most commonly used reactions in medicinal chemistry, multicomponent reactions (MCRs) can lead to the generation of various compounds in a one-step reaction. In particular, the Ugi reaction can easily provide a peptoid library. Thus, we herein report a solution-phase DEL synthesis based on the Ugi reaction. Using 6-(4-nitrophenoxycarbonylamino)hexanoic acid and N-4-nitrophenoxycarbonylglycine as carboxylic acids, peptoids with activated carbamate moieties were obtained as the products of the Ugi reaction. These peptoids were then treated with oligonucleotides bearing a 5′- or 3′-terminal aminohexyl linker to give various oligonucleotide-tagged peptoids in good yields. Moreover, the obtained peptoids could be substituted by a Suzuki cross-coupling reaction and by hydrolysis of the carboxylate ester, followed by condensation with amines. These advances should therefore promote pharmaceutical and medicinal research using DELs.

Graphical abstract: Conjugation of oligonucleotides with activated carbamate reagents prepared by the Ugi reaction for oligonucleotide library synthesis

Supplementary files

Article information

Article type
Paper
Submitted
13 dec 2021
Accepted
15 apr 2022
First published
19 apr 2022
This article is Open Access
Creative Commons BY license

RSC Chem. Biol., 2022,3, 728-738

Conjugation of oligonucleotides with activated carbamate reagents prepared by the Ugi reaction for oligonucleotide library synthesis

R. Kita, T. Osawa and S. Obika, RSC Chem. Biol., 2022, 3, 728 DOI: 10.1039/D1CB00240F

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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