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

Pre-queuosine or queuine (preQ(1)) is a guanine derivative that is involved in the biosynthetic pathway of the hypermodified tRNA nucleoside queuosine (Que). The core structure of preQ(1) is represented by 7-(aminomethyl)-7-deazaguanine (preQ(1) base). Here, we report the synthesis of three preQ(1) base derivatives with complementary (15)N-labeling patterns, utilizing [(15)N]-KCN, [(15)N]-phthalimide, and [(15)N(3)]-guanidine as cost-affordable (15)N sources. Such derivatives are required to explore the binding process of the preQ(1) base to RNA targets using advanced NMR spectroscopic methods. PreQ(1) base specifically binds to bacterial mRNA domains and thereby regulates genes that are required for queuosine biosynthesis.