Syntheses of (15)N-labeled pre-queuosine nucleobase derivatives.

Jasmin Levic,Ronald Micura

doi:10.3762/bjoc.10.199

Abstract

Pre-queuosine or queuine (preQ1) is a guanine derivative that is involved in the biosynthetic pathway of the hypermodified tRNA nucleoside queuosine (Que). The core structure of preQ1 is represented by 7-(aminomethyl)-7-deazaguanine (preQ1 base). Here, we report the synthesis of three preQ1 base derivatives with complementary 15N-labeling patterns, utilizing [15N]-KCN, [15N]-phthalimide, and [15N3]-guanidine as cost-affordable 15N sources. Such derivatives are required to explore the binding process of the preQ1 base to RNA targets using advanced NMR spectroscopic methods. PreQ1 base specifically binds to bacterial mRNA domains and thereby regulates genes that are required for queuosine biosynthesis.

Highlights

The small pyrrolo[2,3-d]pyrimidine 7-(aminomethyl)-7-deazaguanine is a natural product, termed prequeuosine base [1,2]
PreQ1 base binds to bacterial mRNA domains and thereby regulates genes that are required for queuosine biosynthesis
PreQ1 base has attracted considerable attention because this nucleobase binds to bacterial mRNA domains and regulates genes that are required for queuosine biosynthesis, by a so-called riboswitch mechanism [4,5,6,7,8]

Summary

Introduction

The small pyrrolo[2,3-d]pyrimidine 7-(aminomethyl)-7-deazaguanine is a natural product, termed prequeuosine base (preQ1 base) [1,2]. This guanine derivative is involved in the complex biosynthetic pathway of the hypermodified tRNA nucleoside queuosine [3]. The synthesis of preQ1 base has been described first in 1979 by Goto and coworkers from 2-methylthio-6-methoxy-7-methyl-7deazapurine in 13 steps [9]. Another early, but more efficient procedure was reported by Nishimura in 1988 based on the Mannich reaction using dibenzylamine–formaldehyde and 2-acylaminopyrrolo[2,3-d]pyrimidin-4(3H)-one, which resulted in the selective introduction of the dibenzylaminomethyl group

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Conclusion