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Updated: Jan 15, 2026

Synthesis of Wavelength-shifting DNA Hybridization Probes by Using Photostable Cyanine Dyes
Published on: July 6, 2016
Development of an On-DNA Platform Molecule Bearing a Diazidestructure and Its Application to DEL Synthesis
Hiroyuki Miyachi1, Masaki Koshimizu1, Manussada Ratanasak2
1Lead Exploration Unit, Drug Discovery Initiative, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan.
Abstract:
Expanding the chemical space of DNA-encoded libraries (DELs) is desirable for identifying novel bioactive compounds and enhancing hit quality in affinity-based screening. In this study, we designed and synthesized a new on-DNA diazide platform (DAP) molecule that incorporates both aromatic and aliphatic azido groups within a single scaffold. These orthogonal azides exhibit distinct reactivity profiles, enabling a stepwise warhead construction strategy through chemoselective transformations. This approach facilitates greater structural diversity and efficient incorporation of diverse building blocks. A virtual DEL was generated based on this DAP scaffold, and its chemical space was compared with that of bioactive compounds in the ChEMBL database. The analysis revealed that this virtual library occupied a distinct and previously unexplored region of chemical space, highlighting the potential of this DAP-based strategy for discovering structurally novel DEL members with biological relevance.
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Characteristics of the diene
Conformation
The simplest example of a diene is 1,3-butadiene, an acyclic conjugated π system. At room temperature, the molecule exists as a mixture of s-cis and s-trans conformers by virtue of rotation around the carbon–carbon single bond. Although the s-trans isomer is more stable,...